Insulin Modulated Self-Assembled Nanostructures of IAPP Under Amyloid Disease State

Insulin resistance is considered to be the most common cause of type 2 diabetes (T2D) wherein pancreatic β-cells cosecrete islet amyloid polypeptide (IAPP) with insulin and forms amyloid fibrils at low concentrations. Localization of IAPP between the secretory vesicle membrane and the crystal inhibits IAPP fibrillation. Moreover, inhibition of monomeric insulin and lipid membranes accelerate the fibrillation of IAPP in vitro. The present work investigates the interactions in vitro between lipid-IAPP-insulin under amyloid disease state. Fluorescence microscopy is used to investigate insulin’s effect on fibrillation of IAPP and to study the interactions of crystalline insulin with lipids and IAPP but revealed no significant interaction between IAPP and insulin. However, stable insulin-IAPP interactions are apparent in larger assemblies of crystalline insulin or IAPP fibres favouring the chances of various physiological interactions between these two β-cell hormones. The atomic force microscopy and electron microscopy studies indicate that the assembling process of hIAPP fibre can be tuned by the large surface of insulin. Also, the morphology of self-assembled nanostructures of hIAPP is modulated by the effect of insulin. These results are expected to offer a greater understanding of the interactions between insulin, lipids and peptides paving new dimensions in amyloid disease based therapeutics.

Release of insulin from PLGA–alginate dressing stimulates regenerative healing of burn wounds in rats

Bioactive crystalline insulin microencapsulated in a Food and Drug Administration (FDA)-approved co-polymeric substance (poly{lactic-co-glycolic acid}), when released in a sustained manner to burn wounds, stimulated improved healing by reducing stress-related tissue damage, controlling inflammation and enhancing tissue integrity.

Oral insulin in diabetic dogs

ABSTRACT Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1·5–2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1·5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia. Journal of Endocrinology (1991) 131, 267–278

Insulin-Dependent Diabetes Mellitus

Insulin-dependent diabetes mellitus (IDDM), now usually called type I diabetes, is the most common endocrine disorder of childhood and adolescence, affecting at least 1 in 400 youngsters. In addition, the prevalence appears to be increasing, particularly as noted in Scandinavia, where registries for this disease are maintained. During the past 10 to 15 years, astounding advances have been made, both in the treatment of this disease and in understanding its etiology. However, perfect treatment, prevention, and cure of this disease and its long-term sequelae, which include cardiovascular disease, nephropathy requiring dialysis and renal transplantation, neuropathy, and retinopathy, are still lacking. During the next two decades, progress in these areas will surely be made, and the prognosis for children and adolescents with IDDM will continue to improve. Until the discovery of insulin in 1921, virtually all children, adolescents, and young adults with IDDM died within 3 years of disease onset, often reduced to mere skeletons as their weight rapidly decreased secondary to low calorie diets. With the advent of insulin administration, mortality rapidly decreased and expectations increased that, as in other endocrine disorders requiring replacement therapy, diabetes would no longer be a problem after insulin was widely available. Indeed, the use of short-acting regular or crystalline insulin four times per day along with dietary restriction in the 1920s more closely parallels recommendations for control of the disease today than did the modes of therapy in vogue from the 1930s through the middle 1970s.