Effects of oat β-glucan consumption at breakfast on ad libitum eating, appetite, glycemia, insulinemia and GLP-1 concentrations in healthy subjects.

There is evidence that oat β-glucan lowers appetite and ad libitum eating; however, not all studies are consistent, and the underpinning mechanisms are not entirely understood. We investigated the effects of 4 g high molecular weight (MW) oat β-glucan on ad libitum eating, subjective appetite, glycemia, insulinemia and plasma GLP-1 responses in 33 normal-weight subjects (22 female/11 male, mean age (y): 26.9 ± 1.

Mechanisms of toxicity by proinflammatory cytokines in a novel human pancreatic beta cell line, 1.1B4.

Background: Molecular mechanisms of toxicity and cell damage were investigated in the novel human beta cell line, 1.1B4, after exposure to proinflammatory cytokines - IL-1β, IFN-γ, TNF-α.

Methods: MTT assay, insulin radioimmunoassay, glucokinase assay, real time reverse transcription PCR, western blotting, nitrite assay, caspase assay and comet assay were used to investigate mechanisms of cytokine toxicity.

Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia.

The novel human-derived pancreatic β-cell line, 1.1B4 exhibits insulin secretion and β-cell enriched gene expression. Recent investigations of the cellular responses of this novel cell line to lipotoxicity and cytokine toxicity revealed similarities to primary human β cells.

Effects of lipotoxicity on a novel insulin-secreting human pancreatic β-cell line, 1.1B4.

The novel insulin-secreting human pancreatic β-cell line, 1.1B4, demonstrates stability in culture and many of the secretory functional attributes of human pancreatic β-cells. This study investigated the cellular responses of 1.

Configuration of electrofusion-derived human insulin-secreting cell line as pseudoislets enhances functionality and therapeutic utility.

Formation of pseudoislets from rodent cell lines has provided a particularly useful model to study homotypic islet cell interactions and insulin secretion. This study aimed to extend this research to generate and characterize, for the first time, functional human pseudoislets comprising the recently described electrofusion-derived insulin-secreting 1.1B4 human β-cell line.

Development and functional characterization of insulin-releasing human pancreatic beta cell lines produced by electrofusion.

Three novel human insulin-releasing cell lines designated 1.1B4, 1.4E7, and 1.

The role of glucagon- and somatostatin-secreting cells in the regulation of insulin release and beta-cell function in heterotypic pseudoislets.

Background: Pseudoislet studies have concentrated on single beta-cell lines or a combination of insulin and glucagon-secreting cells, overlooking the potential role of somatostatin in insulin release. This study sought to evaluate a heterotypic pseudoislet model containing insulin- (MIN6), glucagon- (αTC1.9) and somatostatin (TGP52)-secreting cells of mouse origin and to compare these pseudoislets with traditional monolayer preparations.

Comparison of insulin release from MIN6 pseudoislets and pancreatic islets of Langerhans reveals importance of homotypic cell interactions.

Objectives: Cellular communication is required for normal patterns of insulin secretion from β cells. Experiments using isolated islets of Langerhans are hampered by lack of supply and the consuming isolation process. Pseudoislets comprising clonal cells have emerged as an alternative to study islet-cell interactions and insulin secretion.

Iterative exposure of clonal BRIN-BD11 cells to ninhydrin enables selection of robust toxin-resistant cells but with decreased gene expression of insulin secretory function.

Objectives: Prevention of pancreatic beta-cell destruction combined with preservation of insulin secretory function is an important goal for cell-based diabetes therapy. This study describes the generation and characteristics of toxin-resistant beta-cells.

Methods: By using iterative exposures to ninhydrin, a new class of robust ninhydrin-tolerant insulin-secreting BRIN-BD11 ninhydrin-tolerant (BRINnt) cells was generated.

Streptozotocin-resistant BRIN-BD11 cells possess wide spectrum of toxin tolerance and enhanced insulin-secretory capacity.

Since streptozotocin (STZ) exhibits beta-cell toxicity, mediated through diverse mechanisms, multiple toxin resistance can be expected in insulin-secretory cells rendered STZ-resistant. RINm5F, but not all cell lines surviving STZ treatment, possess higher insulin content than native parental cells and additional tolerance against alloxan. To understand the impact of STZ tolerant cell selection on toxin resistance and insulin-secretory function, STZ-resistant BRIN-BD11 cells were generated by iterative acute exposure to 20 mM STZ.

Prolonged exposure to homocysteine results in diminished but reversible pancreatic beta-cell responsiveness to insulinotropic agents.

Background: Plasma homocysteine levels may be elevated in poorly controlled diabetes with pre-existing vascular complications and/or nephropathy. Since homocysteine has detrimental effects on a wide diversity of cell types, the present study examined the effects of long-term homocysteine exposure on the secretory function of clonal BRIN-BD11 beta-cells.

Methods: Acute insulin secretory function, cellular insulin content and viability of BRIN-BD11 cells were assessed following long-term (18 h) exposure to homocysteine in culture.

A stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing islet-specific genes and hormones.

Embryonic stem (ES) cells can be differentiated into insulin-producing cells by conditioning the culture media. However, the number of insulin-expressing cells and amount of insulin released is very low. Glucose-dependent insulinotropic polypeptide (GIP) enhances the growth and differentiation of pancreatic beta-cells.

Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes.

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro3)GIP over an 11-day period.

Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice.

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro3)GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro3)GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight.

Effects of long-term exposure to nicotinamide and sodium butyrate on growth, viability, and the function of clonal insulin secreting cells.

The B vitamin nicotinamide (NIC), commonly known as niacin, is currently in trial as a potential means of preventing Type 1 diabetes in first-degree relatives of affected individuals. Sodium butyrate (BUT) a common dietary micronutrient has also been reported to have beneficial effects on the differentiation and function of pancreatic beta cells. Cultured rat insulin-secreting BRIN-BD11 cells were used to investigate the effects of 3 days exposure to NIC (10 mM) and BUT (1 mM) both alone and in combination on beta cell function.

Long-term beneficial effects of vanadate, tungstate, and molybdate on insulin secretion and function of cultured beta cells.

The ultratrace elements vanadate, tungstate, and molybdate exhibit significant antihyperglycemic effects in both type 1 and 2 diabetic animals, but possible effects on the function of pancreatic beta cells are understudied. In the present study, clonal BRIN BD11 cells were cultured for 3 days with each ultratrace element to establish doses lacking detrimental effects on viable beta cell mass. Vanadate treatment (4 micromol/L) had no effect on cellular insulin content but improved glucose-induced insulin secretory responsiveness.

Chronic exposure to tolbutamide and glibenclamide impairs insulin secretion but not transcription of K(ATP) channel components.

Clonal insulin-secreting BRIN-BD11 cells were used to examine effects of chronic 72-144 h exposure to the sulphonylureas tolbutamide and glibenclamide on insulin release, cellular insulin content, and mRNA levels of the Kir6.2 and SUR1 subunits of the beta-cell K(ATP) channel. Chronic exposure for 72-144 h to 5-100 microM tolbutamide and glibenclamide resulted in a time- and concentration-dependent irreversible decline in sulphonylurea-induced insulin secretion.

N-acetyl-GLP-1: a DPP IV-resistant analogue of glucagon-like peptide-1 (GLP-1) with improved effects on pancreatic beta-cell-associated gene expression.

Glucagon-like peptide-1(7-36)amide (GLP-1) is a key insulinotropic hormone with the reported potential to differentiate non-insulin secreting cells into insulin-secreting cells. The short biological half-life of GLP-1 after cleavage by dipeptidylpeptidase IV (DPP IV) to GLP-1(9-36)amide is a major therapeutic drawback. Several GLP-1 analogues have been developed with improved stability and insulinotropic action.

Demonstration of glycated insulin in human diabetic plasma and decreased biological activity assessed by euglycemic-hyperinsulinemic clamp technique in humans.

The presence and biological significance of circulating glycated insulin has been evaluated by high-pressure liquid chromatography (HPLC), electrospray ionization mass spectrometry (ESI-MS), radioimmunoassay (RIA), receptor binding, and hyperinsulinemic-euglycemic clamp techniques. ESI-MS analysis of an HPLC-purified plasma pool from four male type 2 diabetic subjects (HbA(1c) 8.1 +/- 0.