Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs.

Background: Diabetes mellitus is characterized by chronic hyperglycemia with loss of β-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce β-cell regeneration and improve their function in rodents.

Dietary Supplementation with Yerba Mate () Infusion Increases IRS-1 and PI3K mRNA Levels and Enhances Insulin Sensitivity and Secretion in Rat Pancreatic Islets.

"Yerba mate" (YM), an aqueous extract of Ilex paraguariensis, has antioxidant, diuretic, cardio-protective and hypoglycaemic properties. Since its effect on the pancreatic islets remains unclear, we evaluated insulin sensitivity and glucose-stimulated insulin secretion (GSIS) in rats consuming YM or tap water (C) for 21 days. Glucose tolerance, glycemia, triglyceridemia, insulinemia, TBARS and FRAP serum levels were evaluated.

A new analogue of islet neogenesis associated protein with higher structural and plasma stability.

Islet Neogenesis Associated Protein pentadecapeptide (INGAP-PP) increases β-cell mass and function in experimental animals. A short clinical trial also yielded promising results. However, HTD4010, a new peptide derived from INGAP-PP, was developed in order to optimize its specific effects by minimizing its side effects.

Impaired endocrine-metabolic homeostasis: underlying mechanism of its induction by unbalanced diet.

To characterize the intrinsic mechanism by which sucrose induces β-cell dysfunction. Normal rats received for 3 weeks a standard diet supplemented with 10% sucrose in the drinking water (high sucrose (HS)) with/out an antioxidant agent (R/S α-lipoic acid). We measured plasma glucose, insulin, triglyceride, leptin, and lipid peroxidation levels; homeostasis model assessment (HOMA)-insulin resistance (HOMA-IR) and HOMA for β-cell function (HOMA-β) indexes were also determined.

Liver carbohydrates metabolism: A new islet-neogenesis associated protein peptide (INGAP-PP) target.

Islet-Neogenesis Associated Protein-Pentadecapeptide (INGAP-PP) increases β-cell mass and enhances glucose and amino acids-induced insulin secretion. Our aim was to demonstrate its effect on liver metabolism. For that purpose, adult male Wistar rats were injected twice-daily (10 days) with saline solution or INGAP-PP (250 μg).

INGAP-PP effects on β-cell mass and function are related to its positive effect on islet angiogenesis and VEGFA production.

Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances β-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, β-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis.

VMP1-related autophagy induced by a fructose-rich diet in β-cells: its prevention by incretins.

The aim of the present study was to demonstrate the role of autophagy and incretins in the fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed (3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein 1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied.

Role of Islet Glucokinase, Glucose Metabolism, and Insulin Pathway in the Enhancing Effect of Islet Neogenesis-Associated Protein on Glucose-Induced Insulin Secretion.

Objective: To demonstrate the role of islet glucokinase, glucose metabolism, and intracellular insulin mediators in the enhancing effect of islet neogenesis-associated protein pentadecapeptide (INGAP-PP) on glucose-induced insulin secretion.

Methods: Islets from normal rats were cultured for 4 days in the absence or presence of 10 μg/mL INGAP-PP, with/without Wortmannin or LY294002. Islets were incubated with different glucose concentrations to measure insulin secretion and content, hexokinase and glucokinase activity, glucose oxidation and utilization, glucokinase, insulin receptor, insulin receptor substrate (IRS)-1/2, and PI3K concentration and phosphorylation.

Islet NADPH oxidase activity modulates β-cell mass and endocrine function in rats with fructose-induced oxidative stress.

Background: Islet NADPH oxidase activity is modulated by glucose and other insulin secretagogues and it might be part of the regulatory mechanism of insulin secretion. We studied its modulatory role of islet NADPH oxidase upon β-cell function in rats with fructose-induced oxidative stress.

Methods: Normal rats were fed for 3weeks with a standard diet, a fructose-rich diet or both diets plus apocynin.

Islet neogenesis-associated protein (INGAP): the role of its endogenous production as a positive modulator of insulin secretion.

Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches.

Islet cannabinoid receptors: cellular distribution and biological function.

Objectives: This study aimed to determine the cellular distribution of islet cannabinoid receptors (CBs) and their involvement in the development of metabolic and hormonal changes in rats fed a fructose-rich diet (F).

Methods: In normal rat islets, we determined CBs (immunofluorescence and retrotranscription-polymerase chain reaction) and glucose-stimulated insulin secretion (GSIS) of isolated islets incubated with the CB1 antagonist rimonabant (R) and/or different CBs agonists. In 3-week F-fed rats, we determined the in vivo effect of R on serum glucose, triglyceride, and insulin levels; homeostasis model assessment for insulin resistance, GSIS, and CBs and insulin receptor substrate gene expression levels (real-time polymerase chain reaction).