galanin-like-peptide and Diabetes-Mellitus--Type-2

Alarin is a member of the galanin family of neuropeptides that is widely expressed in the central nervous system and peripheral tissues in humans and rodents. It was initially isolated fifteen years ago in ganglionic cells of human neuroblastoma. Subsequently, it was demonstrated to be broadly distributed in the blood vessels, skin, eyes, peripheral and central nervous systems, thymus, gastrointestinal tract, and endocrine organs of different species. Alarin is a 25 amino acid neuropeptide derived from the alternative splicing of the GALP gene, missing exon 3. It is found to be involved in several physiological functions that include feeding behavior, energy homeostasis, glucose homeostasis, body temperature, and reproduction. It has also vasoactive, anti-inflammatory, anti-edema, and antimicrobial activities. However, the physiological effects of alarin have not been fully elucidated and the receptors that mediate these effects are not currently known. Unearthing the novel biological effects of alarin and its unidentified receptors will therefore be a task in future biomedical research. In addition, alarin is involved in various disease conditions, such as metabolic syndrome, obesity, insulin resistance, type 2 diabetes, diabetic retinopathy, hypertension, cardiac fibrosis, polycystic ovarian syndrome, and depression. Thus, alarin may serve as a promising tool for future pharmacological treatment and diagnosis. But further research is awaited to confirm whether alarin has a protective or pathological role in these diseases. This article provides a comprehensive review on the evolving implications of alarin in a variety of physiological and disease conditions, and its future perspectives.

Topics: Amino Acids; Anti-Infective Agents; Anti-Inflammatory Agents; Diabetes Mellitus, Type 2; Galanin; Galanin-Like Peptide; Glucose; Humans; Neuropeptides

Recent preclinical and clinical studies have indicated that the galanin peptide family may regulate glucose metabolism and alleviate insulin resistance, which diminishes the probability of type 2 diabetes mellitus. The galanin was discovered in 1983 as a gut-derived peptide hormone. Subsequently, galanin peptide family was found to exert a series of metabolic effects, including the regulation of gut motility, body weight and glucose metabolism. The galanin peptide family in modulating glucose metabolism received recently increasing recognition because pharmacological activiation of galanin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes mellitus. To date, however, few papers have summarized the role of the galanin peptide family in modulating glucose metabolism and insulin resistance. In this review we summarize the metabolic effect of galanin peptide family and highlight its glucoregulatory action and discuss the pharmacological value of galanin pathway activiation for the treatment of glucose intolerance and type 2 diabetes mellitus.

Topics: Animals; Diabetes Mellitus, Type 2; Female; Galanin; Galanin-Like Peptide; Glucose; Glucose Intolerance; Humans; Insulin Resistance; Male; Mice; Peptide Hormones; Receptors, Galanin; Sex Factors

Insulin resistance, the reciprocal of insulin sensitivity, is known to be a characteristic of type 2 diabetes mellitus, and is regarded as an important mechanism in the pathogenesis. The hallmark of insulin resistance is a gradual break-down of insulin-regulative glucose uptake by muscle and adipose tissues in subjects. Insulin resistance is increasingly estimated in various disease conditions to examine and assess their etiology, pathogenesis and consequences. Although our understanding of insulin resistance has tremendously been improved in recent years, certain aspects of its estimation and etiology still remain elusive to clinicians and researchers. There are numerous factors involved in pathogenesis and mechanisms of insulin resistance. Recent studies have provided compelling clues about some peptides and proteins, including galanin, galanin-like peptide, ghrelin, adiponectin, retinol binding protein 4 (RBP4) and CRP, which may be used to simplify and to improve the determination of insulin resistance. And alterations of these peptide levels may be recognized as risk markers of developing insulin resistance and type 2 diabetes mellitus. This review examines the updated information for these peptides, highlighting the relations between these peptide levels and insulin resistance. The plasma high ghrelin, RBP4 and CRP as well as low galanin, GALP and adiponectin levels may be taken as the markers of deteriorating insulin resistance. An increase in the knowledge of these marker proteins and peptides will help us correctly diagnose and alleviate insulin resistance in clinic and study.

Topics: Adiponectin; Animals; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Disease Progression; Galanin; Galanin-Like Peptide; Ghrelin; Humans; Insulin Resistance; Retinol-Binding Proteins, Plasma; Risk

Alarin has been reported to be relative to food intake and an increase in body weight. However, to date, no report has demonstrated the relationship between circulating alarin and diabetes in humans.. The objective of this study is to gain insight into the possible role of alarin in humans.. 164 patients with newly diagnosed type 2 diabetes mellitus (nT2DM), 112 IGT and 134 healthy subjects were recruited for this study. In an interventional study, 29 nT2DM patients were treated by a weekly GLP-1RA for 6 months. Plasma alarin concentrations were measured by ELISA.. Circulating alarin concentrations were significantly higher in both IGT and nT2DM subjects than in healthy individuals (0.40 ± 0.14 and 0.54 ± 0.24 vs 0.37 ± 0.10 μg/L, P < .05 or P < .01), whereas in T2DM patients, circulating alarin levels were higher than in IGT subjects. Circulating alarin positively correlated with FBG, HbA1c, HOMA-IR, AUCglucose and TNFα (P < .05 or P < .01). Multivariate logistic regression revealed that circulating alarin levels were correlated with IGT and T2DM. GLP-1RA treatment for 6 months increased circulating alarin levels in T2DM patients (from 0.34 ± 0.10 for baseline, to 0.39 ± 0.14 for 12 weeks, and finally to 0.38 ± 0.15 μg/L for 24 weeks; vs. pre-treatment P < .05).. These data suggest that alarin might be involved in the pathogenesis of T2DM in humans.. ChiCTR-OCS-13003185 (18/03/2013 ).

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Cytokines; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Galanin-Like Peptide; Glucagon-Like Peptide-1 Receptor; Glucose Tolerance Test; Humans; Hypoglycemic Agents; Male; Middle Aged; Treatment Outcome

Diabetic retinopathy is a disease seen with microvascular complications as a result of hyperglycemia and insulin resistance. Alarin and Adipsin are molecules with a role in energy and glucose metabolism. The aim of this study was to determine plasma and aqueous levels of Alarin and Adipsin in patients with and without diabetic retinopathy to evaluate their potential roles in diabetic retinopathy.. The study included one eye from each of 20 cataract patients without diabetes (C), 20 cataract patients with diabetes and without diabetic retinopathy (DM + C), and 20 cataract patients with diabetes and diabetic retinopathy (DR + C). Plasma and aqueous humour samples were taken from all patients during the cataract operation. Alarin and Adipsin levels were examined with the enzyme-linked immunosorbent assay (ELISA) method.. Both plasma and aqueous Alarin levels were significantly higher in the patients with diabetic retinopathy than in the control group (p < 0.001, p = 0.006). Adipsin levels were found to be significantly higher in plasma in the control group than in the DR + C group and significantly higher in aqueous in the DR + C group than in the control group (p < 0.001, p < 0.001).. These findings suggest that Alarin and Adipsin may play important role in diabetic retinopathy.

Topics: Aqueous Humor; Cataract; Complement Factor D; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Galanin-Like Peptide; Humans

Alarin, a regulatory peptide, belongs to the galanin family and plays the same regulatory roles as galanin in orexigenic activity and energy metabolism. Our previous studies had found that galanin might facilitate insulin sensitivity via activation of its central receptors. To date, little is known about whether central alarin may exert similar effects on insulin sensitivity. In order to investigate this, alarin and its specific antagonist, alarin 6-25Cys, were administered into the cerebral ventricles of type 2 diabetic rats (T2DR) to evaluate the changes in insulin resistance. The results indicated that central treatment with alarin significantly increased the body weight of animals, the 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake, the plasma adiponectin levels, the glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, the vesicle-associated membrane protein 2 as well as glucose transporter 4 (GLUT4 (SLC2A4)) protein and mRNA levels, and the ratios of GLUT4 contents in plasma membranes to total cell membranes in adipocytes, but reduced blood glucose and plasma retinol-binding protein 4 levels. These effects of alarin may be inhibited by pretreatment with alarin 6-25Cys. The above-mentioned results suggest that the central alarin projective system may facilitate insulin sensitivity and glucose uptake via the increase in GLUT4 content and GLUT4 translocation from intracellular pools to plasma membranes in T2DR.

Topics: 4-Chloro-7-nitrobenzofurazan; Adipocytes; Adiponectin; Animals; Blood Glucose; Blotting, Western; Body Weight; Cell Membrane; Deoxyglucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Galanin-Like Peptide; Gene Expression; Glucose Transporter Type 4; Injections, Intraventricular; Insulin Resistance; Male; Peptide Fragments; Protein Transport; Rats, Wistar; Retinol-Binding Proteins, Plasma; Reverse Transcriptase Polymerase Chain Reaction; Vesicle-Associated Membrane Protein 2