insulin--isophane and Inflammation

Acute hyperglycaemia exerts deleterious effects on the arterial wall. We suggested that rapid-acting insulin has a beneficial postprandial effect on endothelial dysfunction and inflammation compared with intermediate-acting insulin because of its ability to lower postprandial hyperglycaemia. This was tested in a parallel, controlled study on well-controlled patients with type 2 diabetes randomly assigned to bedtime Neutral Protamine Hagedorn (NPH) insulin (n = 41) or mealtime insulin aspart (n = 37). They were served standard diabetic meals for breakfast (8.00) and lunch (12.00). Blood samples were collected at 7.40 (fasting), 9.30, 11.30, 13.30 and 15.30 and analysed for glucose, insulin, lipids, intercellular adhesion molecules (ICAM), C-reactive protein (CRP), von Willebrand factor (vWF) and fibrinogen. The postprandial glucose response differed significantly between insulin regimens with a postprandial increase on NPH insulin and a decrease on insulin aspart. There was a minor but significant postprandial decrease in ICAM, CRP and vWF on both insulin regimens and a decrease in fibrinogen on NPH insulin. No insulin group differences were observed in postprandial responses for ICAM, CRP, vWF and fibrinogen. The rapid-acting insulin analogue aspart and the intermediate-acting insulin NPH had different effects on postprandial glucose response but similar postprandial effects on markers of inflammation and endothelial dysfunction.

Topics: Aged; Biomarkers; Cell Adhesion Molecules; Diabetes Mellitus, Type 2; Endothelial Cells; Female; Food Deprivation; Humans; Inflammation; Insulin Aspart; Insulin, Isophane; Male; Middle Aged; Postprandial Period; Sleep; von Willebrand Factor

Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injections. Previous studies have shown poor bioavailability (less than 15%) with nasal insulin administration with various absorption enhancers. The aim of the study was to evaluate in type 1 diabetic patients, the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters.. The study was conducted in 16 type 1 diabetic patients (HbA1c 8.6+/-0.2%) in a cross-over trial including 2 six month randomized periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily + 3 pre-prandial regular insulin injections. End points were HbA1c levels, hypoglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clinical symptoms and objective nasal assessments.. Four patients were withdrawn because of nasal burning (3 cases) and persistent sinusitis (1 case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM, NS) for nasal and subcutaneous period respectively. The number of hypoglycaemic events was identical during the 2 periods (88 episodes). Nasal tolerance with the gelified form was better than with the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance.. 1) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients. 2) Other galenic forms should be investigated to improve nasal tolerance and bioavailability.

Topics: Administration, Intranasal; Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Inflammation; Injections, Subcutaneous; Insulin, Isophane; Nasal Mucosa; Sinusitis

Erectile dysfunction (ED) is a distressing complication in men with diabetes mellitus (DM). This study aimed to investigate the effects of adipose-derived stem cells (ADSCs) plus insulin on ED in streptozotocin (STZ)-induced diabetic rats.. Forty-five eight-week-old male Sprague-Dawley rats received intraperitoneal injection of STZ (60 mg/kg). Eight weeks after the induction, the determined diabetic rats were randomly distributed into four groups: rats in DM + PBS group received a one-time intracavernous (IC) injection of phosphate-buffered saline (PBS) solution, DM + ADSCs group received IC injection of ADSCs, DM + Insulin group received subcutaneous injection of neutral protamine Hagedorn twice a day, and DM + ADSCs + Insulin group received both ADSCs and neutral protamine Hagedorn treatments. Another 10 normal rats were served as control group and received IC injection of PBS. Four weeks after the treatments, intracavernous pressure, histopathological changes in penis, functional proteins of ADSCs, and penis were measured.. We found that ADSCs expressed vascular endothelial growth factor, TIMP metallopeptidase inhibitor 1 (TIMP-1), and lipopolysaccharide-inducible CXC chemokine (LIX). ADSC injection partially restored cavernous endothelium and smooth muscle contents and nNOS-positive nerves, and reduced apoptosis in penis compared with PBS-treated diabetic rats. Insulin treatment could further modulate inflammatory response and reduce advanced glycation end-product accumulation in penis.. Better than single therapy, ADSCs combined with insulin ameliorate ED and pathological changes in diabetic rats to near-normal levels.

Topics: Adipose Tissue; Animals; Apoptosis; Chemokine CXCL5; Combined Modality Therapy; Diabetes Mellitus, Experimental; Erectile Dysfunction; Glycation End Products, Advanced; Hypoglycemic Agents; Inflammation; Insulin, Isophane; Male; Nitric Oxide Synthase Type I; Penis; Peripheral Nerves; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Stem Cell Transplantation; Stem Cells; Tissue Inhibitor of Metalloproteinase-1; Vascular Endothelial Growth Factor A

As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of both is correspondingly expected to occur frequently. To examine whether insulin influences the development of inflammation in the alveolar septa, diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were used. Ten days after alloxan injection, diabetic and control rats were instilled with physiologic saline solution containing porcine pancreatic elastase (PPE, 0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL) fluid of the animals, 6 h after PPE/saline instillation (early time point); and (ii) mean alveolar diameter (μm) and quantification of elastic and collagen fibres (%) 50 days after PPE/saline instillation (late time point). Relative to controls, alloxan-induced diabetic rats showed a 42% reduction in the number of neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33% decrease in elastic fibre density in the alveolar septa. Treatment of diabetic rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase instillation, restored the number of neutrophils in the BAL fluid. The mean alveolar diameter and elastic fibre content in alveolar septa matched the values observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h before instillation followed by 2 IU/day for the next 50 days. Density of collagen fibres did not differ between the various groups. Thus, the data presented suggest that insulin modulates the inflammatory and repair responses in elastase-induced emphysema, and assures normal repair and tissue remodelling.

Topics: Alloxan; Animals; Blood Glucose; Cell Movement; Collagen; Comorbidity; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Elastic Tissue; Inflammation; Insulin; Insulin, Isophane; Leukocytes; Male; Pancreatic Elastase; Pulmonary Emphysema; Rats; Rats, Wistar