vasoactive-intestinal-peptide and Diabetes-Mellitus

In this review, we discuss sympathetic regulation in normal and diabetic wound healing. Experimental denervation studies have confirmed that sympathetic nerve endings in skin have an important and complex role in wound healing. Vasoconstrictor neurons secrete norepinephrine (NE) and neuropeptide Y (NPY). Both mediators decrease blood flow and interact with inflammatory cells and keratinocytes. NE acts in an ambiguous way depending on receptor type. Beta2-adrenoceptors could be activated near sympathetic endings; they suppress inflammation and re-epithelialization. Alpha1- and alpha2-adrenoceptors induce inflammation and activate keratinocytes. Sudomotor neurons secrete acetylcholine (ACh) and vasoactive intestinal peptide (VIP). Both induce vasodilatation, angiogenesis, inflammation, keratinocytes proliferation and migration. In healthy skin, all effects are important for successful healing. In treatment of diabetic ulcers, mediator balance could be shifted in different ways. Beta2-adrenoceptors blockade and nicotinic ACh receptors activation are the most promising directions in treatment of diabetic ulcers with neuropathy, but they require further research.

Topics: Acetylcholine; Diabetes Complications; Diabetes Mellitus; Hemodynamics; Humans; Inflammation; Neurons; Neuropeptide Y; Norepinephrine; Receptors, Adrenergic; Skin; Skin Ulcer; Sympathetic Nervous System; Vasoactive Intestinal Peptide; Vasoconstriction; Wound Healing

Type 2 diabetes (T2D) is characterized by chronic insulin resistance and a progressive decline in beta-cell function. Although rigorous glucose control can reduce morbidity and mortality associated with diabetes, achieving optimal long-term glycemic control remains to be accomplished in many diabetic patients. As beta-cell mass and function inevitably decline in T2D, exogenous insulin administration is almost unavoidable as a final outcome despite the use of oral antihyperglycemic agents in many diabetic patients. Pancreatic islet cell death, but not the defect in new islet formation or beta-cell replication, has been blamed for the decrease in beta-cell mass observed in T2D patients. Thus, therapeutic approaches designed to protect islet cells from apoptosis could significantly improve the management of T2D, because of its potential to reverse diabetes not just ameliorate glycemia. Therefore, an ideal beta-cell-preserving agent is expected to protect beta cells from apoptosis and stimulate postprandial insulin secretion along with increasing beta-cell replication and/or islet neogenesis. One such potential agent, the islet endocrine neuropeptide vasoactive intestinal peptide (VIP) strongly stimulates postprandial insulin secretion. Because of its broad spectrum of biological functions such as acting as a potent anti-inflammatory factor through suppression of Th1 immune response, and induction of immune tolerance via regulatory T cells, VIP has emerged as a promising therapeutic agent for the treatment of many autoimmune diseases including diabetes.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Insulin-Secreting Cells; Pituitary Adenylate Cyclase-Activating Polypeptide; Vasoactive Intestinal Peptide

Neuropeptides are expressed in neurons innervating endocrine cells or in endocrine cells and cancer cells, and are released on site to act as hormones and growth factors. Vasoactive intestinal peptide (VIP) was first discovered in the early 1970s and has since become the area of research for many laboratories. VIP has a neuroendocrine role as it is intimately involved with the synthesis, secretion and action of other neuroendocrine hormones as well as cytokines and chemokines. Major outcomes of VIP downregulation encompass developmental and behavioral dysfunctions, including impaired diurnal rhythms. Overexpression of VIP has been associated with diarrhea and cancer, and overexpression of VIP receptors is associated with cancerous growth. This short review outlines some of the recent progress made in VIP research.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular System; Diabetes Mellitus; Gastrointestinal Agents; Humans; Neuroprotective Agents; Receptors, Vasoactive Intestinal Peptide; Signal Transduction; Vasoactive Intestinal Peptide

Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions.

Topics: Acetylcholine; Aging; Animals; Biological Transport, Active; Blood-Brain Barrier; Brain; Capillaries; Capillary Permeability; Cerebrovascular Circulation; Cholecystokinin; Diabetes Mellitus; Dopamine; Endothelium; Histamine; Hypertension; Hypoxia, Brain; Locus Coeruleus; Microcirculation; Neural Pathways; Neurons; Norepinephrine; Receptors, Neurotransmitter; Serotonin; Substance P; Vasoactive Intestinal Peptide

Topics: Adrenocorticotropic Hormone; Adult; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Erectile Dysfunction; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteinizing Hormone; Male; Melanocyte-Stimulating Hormones; Middle Aged; Prolactin; Reproduction; Sexual Dysfunction, Physiological; Thyrotropin-Releasing Hormone; Urodynamics; Vasoactive Intestinal Peptide

Topics: Diabetes Mellitus; Gastrins; Humans; Pancreatic Hormones; Pancreatic Neoplasms; Peptic Ulcer; Somatostatin; Vasoactive Intestinal Peptide

The pathology, aetiology and clinical features of cystic fibrosis (CF) are briefly reviewed. The diffuse endocrine system (DES) may be involved in either a primary or secondary manner. Carbohydrate intolerance is common and the release of islet hormones is deficient, as is the release of the intestinal hormone gastric inhibitory polypeptide (GIP). The post-prandial responses of insulin and GIP can be improved by substituting an elemental meal, suggesting that malabsorption and local intestinal factors could be causative in the deficient responses. Vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cell numbers are increased in CF and an intimate association with mucous cells is noted suggesting a paracrine relationship. These findings could have implications in the diagnosis, management and aetiology of CF.

Topics: Atrophy; Cystic Fibrosis; Diabetes Mellitus; Endocrine Glands; Food; Gastric Inhibitory Polypeptide; Glucagon; Histocytochemistry; Humans; Insulin; Jejunum; Pancreas; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

Information concerning GEP hormones has progressively advanced since the initial discovery of a GEP hormone, secretin, in 1902. Studies in this area flourished with the advent of radioimmunoassay, and have provided an understanding of the secretion, regulation, metabolic actions, and role in certain diseases of major GEP hormones. Measurement of GEP hormones has achieved importance in clinical medicine and allowed understanding of the pathophysiology of several clinical disorders. The decade to come should witness additional advances in this rapidly expanding field.

Topics: Chemical Phenomena; Chemistry; Cholecystokinin; Diabetes Mellitus; Diarrhea; Endocrine System Diseases; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypoglycemia; Motilin; Neoplasms; Neurotensin; Pancreatic Polypeptide; Peptic Ulcer; Secretin; Skin Diseases; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Carbohydrate Metabolism; Cholecystokinin; Diabetes Mellitus; Digestion; Gastrointestinal Hormones; Glucagon; Humans; Radioimmunoassay; Secretin; Somatostatin; Vasoactive Intestinal Peptide

Despite the prevalence of diabetic retinopathy, the majority of adult diabetic patients develop visually debilitating corneal complications, including impaired wound healing. Unfortunately, there is limited treatment for diabetes-induced corneal damage. The current project investigates a novel, peptide-based combination therapy, thymosin beta-4 and vasoactive intestinal peptide (Tβ4/VIP), against high-glucose-induced damage to the corneal epithelium. Electric cell-substrate impedance sensing (ECIS) was used for real-time monitoring of barrier function and wound healing of human corneal epithelial cells maintained in either normal glucose (5 mM) or high glucose (25 mM) ± Tβ4 (0.1%) and VIP (5 nM). Barrier integrity was assessed by resistance, impedance, and capacitance measurements. For the wound healing assay, cell migration was also monitored. Corneal epithelial tight junction proteins (ZO-1, ZO-2, occludin, and claudin-1) were assessed to confirm our findings. Barrier integrity and wound healing were significantly impaired under high-glucose conditions. However, barrier function and cell migration significantly improved with Tβ4/VIP treatment. These findings were supported by high-glucose-induced downregulation of tight junction proteins that were effectively maintained similar to normal levels when treated with Tβ4/VIP. These results strongly support the premise that Tβ4 and VIP work synergistically to protect corneal epithelial cells against hyperglycemia-induced damage. In addition, this work highlights the potential for significant translational impact regarding the treatment of diabetic patients and associated complications of the cornea.

Topics: Diabetes Mellitus; Epithelial Cells; Glucose; Humans; Hyperglycemia; Tight Junction Proteins; Vasoactive Intestinal Peptide

To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus (DM).. Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson's Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), neurokinin-1 (NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha, (PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also conducted.. Twenty-six controls and 35 diabetic patients (21 short-duration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index (BMI) (higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group (. Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

Topics: Aged; Case-Control Studies; Diabetes Mellitus; Enteric Nervous System; Female; Fluorescent Antibody Technique; Gastric Mucosa; Humans; Immunohistochemistry; Male; Microscopy, Confocal; Middle Aged; Muscle, Smooth; Nitric Oxide Synthase Type I; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Receptors, Neurokinin-1; Stomach; Telocytes; Time Factors; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Impaired pregnancy in non-obese diabetic (NOD) mice was related to limited vascular remodeling and autoimmune background. Vasoactive intestinal peptide (VIP) has anti-inflammatory and immunosuppressant effects, so we explored its ability to modulate the immune microenvironment at the early maternal-placental interface and improve pregnancy in NOD mice.. Implantation sites were isolated from pregnant NOD mice at gestational day 9.5 and were incubated with VIP for evaluation of cytokine or transcription factor expression by RT-PCR, immunoblotting, and immunohistochemistry. Alternatively, pregnant mice were injected with VIP at day 6.5 and studied at day 9.5.. VIP and VPAC receptors were detected in viable implantation sites. VIP immunostaining was found predominantly on trophoblast giant cells. The in vitro treatment of viable implantation sites with VIP increased IL-10, TGF-β, and Foxp3 expression. Sites with resorption processes presented lower VIP expression, reduced suppressant markers, and increased IL-17 and RORγT expression compared with viable sites and VIP reduced RORγT expression. Pregnant mice treated with VIP at day 6.5 presented an even distribution of viable implantation sites with an increased expression of IL-10, TGF- β, and Foxp3.. VIP induces an immunosuppressant profile at the early maternal-placental interface of NOD mice and improves pregnancy outcome.

Topics: Animals; Cells, Cultured; Cellular Microenvironment; Cytokines; Diabetes Mellitus; Disease Models, Animal; Female; Forkhead Transcription Factors; Gestational Age; Humans; Immune Tolerance; Maternal-Fetal Exchange; Mice; Mice, Inbred NOD; Nuclear Receptor Subfamily 1, Group F, Member 3; Organ Culture Techniques; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Receptors, Vasoactive Intestinal Peptide, Type II; Uterus; Vasoactive Intestinal Peptide

Studies focused on the development of diabetes in NOD mice-a model for human type 1 diabetes-have revealed that an autoimmune inflammatory process is produced by the effect of Th1 cells and their secreted cytokines. DNA vaccination has been shown to be an effective method for modulating immunity in viral infections and experimental autoimmune diseases, including diabetes. VIP's immunomodulatory properties are partly mediated by skewing the pattern of cytokines from a proinflammatory response to an anti-inflammatory response. Using gene delivery to express VIP, we interfered in the immune process leading to diabetes in prone, cyclophosphamide-treated NOD mice. Our results extend the role of VIP in the control of immunoregulatory networks and open new perspectives for immunointervention through VIP-based gene therapy.

Topics: Animals; Diabetes Mellitus; Female; Gene Transfer Techniques; Mice; Mice, Inbred NOD; Plasmids; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent with immunoregulatory properties, skewing the immune response to a Th2 pattern of cytokine production. Here, we studied the effect of treatment with VIP in the development of diabetes in nonobese diabetic (NOD) mice, an animal model of type 1 diabetes. Mice treated with VIP from 4 weeks of age did not develop diabetes and showed milder insulitis than nontreated mice. The protective mechanism of VIP was associated with a reduction in the circulating levels of Th1 cytokines. In the pancreas of VIP-treated animals, regulatory T cell markers predominate, as indicated by the upregulation of FoxP3 and transforming growth factor-beta (TGF-beta), and the downregulation of the transcription factor, T-bet. These findings indicate that VIP restores tolerance to pancreatic islets by promoting the local differentiation and function of regulatory T cells.

Topics: Animals; Autoimmunity; Cell Proliferation; Diabetes Mellitus; Female; Forkhead Transcription Factors; Immune Tolerance; Insulin; Mice; Mice, Inbred NOD; Pancreas; Th1 Cells; Th2 Cells; Transforming Growth Factor beta; Vasoactive Intestinal Peptide

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.

Topics: Adolescent; Adult; Atrophy; Biopsy; Blood Glucose; Chronic Disease; Diabetes Mellitus; Female; Gastrins; Glucagon; Humans; Hyperplasia; Immunohistochemistry; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Polypeptide; Pancreatitis; Vasoactive Intestinal Peptide

Twelve pre-diabetic and 12 diabetic female NOD mice aged 22-24 weeks were studied. As controls, 12 female BALB/cJ of the same age and sex were used. The duodenal content of several neuropeptides, namely vasoactive intestinal polypeptide (VIP), neurotensin, neuropeptide Y (NPY), galanin, gastrin-releasing peptide (GRP) and enkephalin was determined by radioimmunoassay of tissue extracts. The VIP content in duodenal extracts from both pre-diabetic and diabetic NOD mice was significantly higher than that of the controls. The enkephalin content of the duodenum of diabetic mice was significantly higher than that of the controls, while no significant difference was found between the controls and pre-diabetic mice. There was no statistically significant difference between controls and NOD mice regarding the duodenal content of neurotensin, NPY, galanin or GRP. It has been suggested that the high duodenal content of VIP appears to be primary to the onset of diabetes and that the high enkephalin content may be attributable to the diabetic state. The changes in the duodenal content of VIP and enkephalin reported here in an animal model for diabetes type I might be of relevance for the gastrointestinal complications occurring in human diabetes.

Topics: Animals; Diabetes Mellitus; Duodenum; Female; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Neuropeptides; Reference Values; Vasoactive Intestinal Peptide

Complications of diabetes include sensory and autonomic neuropathy. The aim of the present paper was to study the degree of sensory and autonomic neuropathy and correlate these findings with the distribution and density of neuropeptidergic nerve fibers in the skin of the forearm of diabetic patients and healthy controls. We investigated 30 diabetics (24 type 1 and 6 type 2) and compared them with 13 healthy controls. There were no differences between the groups with respect to density and distribution of nerve fibers displaying immunoreactivity to the pan-neuronal marker PGP 9.5 and sensory and parasympathetic neuropeptides (substance P, calcitonin gene-related peptide and vasoactive intestinal peptide). By contrast, nerve fibers containing neuropeptide Y, a marker of sympathetic neurons, were reduced in number in the diabetic patients. C-fiber function (measured as the axon-reflex-evoked flare response) became impaired with increasing age in all subjects. The diabetic patients, however, showed a reduced flare compared to age-matched healthy controls. The reduction was particularly prominent in the younger patients (20-50 years). There was a greater reduction of the flare in neuropathic patients than in non-neuropathic patients, but there was no correlation between the degree of functional impairment and the duration of the disease.

Topics: Adult; Aged; Autonomic Nervous System; Axons; Calcitonin Gene-Related Peptide; Case-Control Studies; Diabetes Mellitus; Diabetic Neuropathies; Female; Forearm; Humans; Male; Middle Aged; Nerve Fibers; Neurons, Afferent; Neuropeptide Y; Parasympathetic Nervous System; Skin; Substance P; Sympathetic Nervous System; Thiolester Hydrolases; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Histochemical, immunohistochemical and neurochemical techniques were used to examine the innervation of epineurial nerve sheaths and fascicular nerve bundles of human sural and optic nerves from controls and patients with peripheral neuropathy due to diabetes or alcoholism. The normal distribution of autonomic nerves in both nerve trunk sheaths consisted of a dense innervation by noradrenaline (NA)-containing nerves of the vasa nervorum, together with some fibres in the nervi nervorum. Intrafascicular NA-containing nerves were only present in the sural nerve. Vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing nerves also innervated the vasa nervorum and nervi nervorum of the nerve sheaths, although their density was considerably less. Substance P (SP)-containing nerves were sparse and primarily intrafascicular. Neurochemical assays for NA, VIP, NPY and SP in fascicular and epineurial preparations from the sural and optic nerves confirmed the light microscopical observations. Post mortem delay significantly affected the NA levels in the sural nerve but not in the optic nerve while the NA fascicular/epineurial ratio for the sural nerve was independent of this factor. Age, sex and the presence of alcohol at time of death had no effect on transmitter levels in normal sural nerves. In the optic nerve fascicles NA levels were higher in females than in males. In patients with peripheral neuropathy there was a significant reduction in the SP fascicular/epineurial ratio in both the optic nerve, which was histologically normal, and in the sural nerve, where there was evidence of neuropathy. The NA fascicular/epineurial ratio was also significantly reduced in the sural nerve from patients with peripheral neuropathy with a possible greater effect in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Alcoholism; Autopsy; Diabetes Mellitus; Female; Histocytochemistry; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Fibers, Myelinated; Neuropeptide Y; Neuropeptides; Norepinephrine; Optic Nerve; Substance P; Sural Nerve; Vasoactive Intestinal Peptide

Immunocytochemistry for the general neuronal marker protein gene product 9.5 and four neuropeptides (calcitonin gene-related peptide, substance P, vasoactive intestinal polypeptide and neuropeptide Y) was performed on 20 skin biopsy specimens from 19 diabetic patients, age range 20-75 years, 17 Type 2 (non-insulin-dependent) and 3 Type 1 (insulin-dependent). Fifteen specimens were from the lower limb, 3 from the upper limb and 2 from the abdominal wall. Seven subjects had lower limb neurophysiological tests. All but one specimen showed reduced protein gene product 9.5 and neuropeptide immunoreactivity. Reduced protein gene product 9.5 and neuropeptide immunoreactivity was found in specimens taken from the abdominal wall and hand as well as those from the leg, and also in specimens from patients undergoing amputation for peripheral vascular disease. In general, the greater the number of abnormal neurophysiological tests, the greater the extent of neuronal abnormalities. Three patients with normal tests had abnormalities of dermal innervation. While these changes are also found in other axonal neuropathies, in the absence of other causes of peripheral nerve disease and of macrovascular disease, immunocytochemistry of skin biopsies may have a role in the assessment of diabetic neuropathy and its response to treatment.

Topics: Adult; Aged; Biopsy; Calcitonin Gene-Related Peptide; Diabetes Mellitus; Diabetic Neuropathies; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Skin; Substance P; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide

Topics: Carbohydrate Metabolism; Diabetes Mellitus; Gastric Inhibitory Polypeptide; Glucagon; Humans; Pancreatic Hormones; Somatostatin; Vasoactive Intestinal Peptide

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chronic Disease; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Pancreatitis; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Plasma vasoactive intestinal peptide (VIP) concentrations of normal individuals and patients with pancreatitis were studied using a VIP RIA kit. The inter-assay and intra-assay variation of this kit were between 2.1 and 9.4%. The VIP levels increased in the acute phase of acute pancreatitis and patients with chronic pancreatitis. The VIP concentration increased during the first 30 min of glucose tolerance test, but this increase was much smaller than that in insulin. These results suggest that this kit is useful for physiologic and pathologic changes in the VIP level.

Topics: Diabetes Mellitus; Glucose Tolerance Test; Humans; Insulin; Pancreatic Neoplasms; Pancreatitis; Radioimmunoassay; Vasoactive Intestinal Peptide

Topics: Diabetes Mellitus; Diabetic Retinopathy; Female; Humans; Male; Neutrophils; Vasoactive Intestinal Peptide

The concentrations and contents of immunoreactive substance P (SP), neurokinin A (NKA), vasoactive intestinal polypeptide (VIP) and gastrin releasing peptide (GRP) were measured in acid-ethanol extracts of intestine (duodenum-jejunum-ileum) and pancreas of C57BL/KsJ diabetes-obese (db/db) mice, Aston obese-hyperglycaemic (ob/ob) mice, and their respective lean controls. The intestinal concentration of GRP and pancreatic concentrations of VIP and GRP were 36-57% lower in lean Aston mice than lean C57BL/KsJ mice, indicating the influence of genetic background in control mice. Intestinal concentrations of SP and NKA were reduced by 19-33% in the db/db and ob/ob mutants compared with their lean controls, but the intestinal contents of these peptides were normal or greater than normal due to intestinal hypertrophy of the mutant mice. The intestinal VIP concentration was not altered, but the content was increased by 87% and 25% respectively in db/db and ob/ob mice, whereas the intestinal GRP concentration was reduced by 51% in ob/ob mice. Pancreatic concentrations and contents of NKA, VIP and GRP were similar in lean and db/db C57BL/KsJ mice. However, pancreatic concentrations and contents of VIP and GRP were reduced by 51-55% in ob/ob mice compared with their lean controls. The sensitivity of the present assay did not permit accurate determination of the low pancreatic concentrations of SP. The results suggest that the spontaneous ob/ob and db/db syndromes of obesity and diabetes in mice are associated with reduced intestinal concentrations of SP and NKA. The ob/ob mouse also exhibited reductions of intestinal GRP and pancreatic GRP and VIP concentrations. These changes in regulatory peptides may relate to abnormalities of intestinal and possibly pancreatic function in obese and diabetic mutant mice.

Topics: Animals; Diabetes Mellitus; Gastrin-Releasing Peptide; Insulin; Insulin Secretion; Intestines; Mice; Mice, Inbred C57BL; Mice, Obese; Mutation; Neurokinin A; Neuropeptides; Obesity; Pancreas; Peptides; Substance P; Vasoactive Intestinal Peptide

Somatostatin-like and avian pancreatic polypeptide-like immunoreactivities were found to occur within certain cellular elements of the dermis of a patient having diabetic lipodystrophic skin lesions. No specific immunofluorescence could be seen in the epidermis.

Topics: Adult; Diabetes Mellitus; Enkephalin, Methionine; Fluorescent Antibody Technique; Humans; Lipodystrophy; Male; Pancreatic Polypeptide; Peptides; Skin; Somatostatin; Substance P; Thyrotropin-Releasing Hormone; Vasoactive Intestinal Peptide

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus; Enkephalins; Esophageal Achalasia; Esophageal Neoplasms; Esophagogastric Junction; Female; Hernia, Hiatal; Histocytochemistry; Humans; Male; Middle Aged; Nerve Tissue Proteins; Radioimmunoassay; Substance P; Vasoactive Intestinal Peptide

Topics: Animals; Diabetes Mellitus; Endocrine System Diseases; Gastrins; Heart; Hormones; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Ketone Bodies; Myocardium; Periodicity; Rats; Receptor, Insulin; Receptors, Adrenergic, beta; Receptors, Muscarinic; Somatostatin; Vasoactive Intestinal Peptide

Topics: Adenoma, Islet Cell; Adult; Aged; Diabetes Mellitus; Diagnosis, Differential; Female; Glucagonoma; Humans; Insulinoma; Liver Neoplasms; Male; Middle Aged; Pancreatic Neoplasms; Skin Diseases; Somatostatinoma; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) has been demonstrated by immunofluorescence histochemistry in nerves in human and rat penile tissue. A reduction in VIP-like immunoreactivity in nerves was revealed in tissue from streptozotocin-diabetic rats and a human diabetic with impotence. These results suggest that an impairment in the VIP-ergic innervation in penile tissue may be an important factor in the development of impotence in diabetes. They also support the view that the streptozotocin-treated rat is a useful experimental model for diabetic autonomic neuropathy.

Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Erectile Dysfunction; Fluorescent Antibody Technique; Humans; Male; Penis; Rats; Vasoactive Intestinal Peptide

Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immunocytochemical testing showed that antibody-positive diabetic plasma reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity and naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

Topics: Adolescent; Adult; Aged; Animals; Autoantibodies; Child; Diabetes Mellitus; Drug Contamination; Gastrointestinal Hormones; Glucagon; Hormones; Humans; Insulin; Middle Aged; Pancreatic Polypeptide; Sheep; Somatostatin; Swine; Vasoactive Intestinal Peptide