Exendin-4 Increases Islet Amyloid Deposition But Offsets The Resultant

Therefore, while exendin-4 does result in increased amyloidogenesis, it also appears to offset the toxic effects of amyloid deposition by limiting beta-cell apoptosis, resulting in beta-cell preservation.

IAPP release is necessary for islet amyloid formation and its toxic effects, and use of insulin secretagogues to treat type 2 diabetes may result in increased isletAmyloidogenesis and beta cell death, but the AKT-associated anti-apoptotic effects of GLP-1 receptor agonists such as exendin-4 may limit the toxic effects of increased iseloid formation. Aims/hypothesisIn type 2 diabetes ...

As we can see from the illustration, Exendin-4 Increases Islet Amyloid Deposition But Offsets The Resultant has many fascinating aspects to explore.

Islets were isolated from 10-week-old hemizygous F1 C57BL/6 DBA/2J human IAPP transgenic mice and their non-transgenic littermates, as previously described . Principles of laboratory animal care (NIH publication no. 85-23, revised 1985; http://grants1.nih.gov/grants/olaw/references/phspol.htm) were followed. Animal studies were approved by the ... See full list on link.springer.com We have previously shown that amyloid is detectable as early as 24 h after culture in 16.7 mmol/l glucose, its deposition increasing progressively over 144 h . To determine the optimal culture time for the current study, islets were cultured for 144 h with or without exendin-4 with samples taken at 48 h intervals. In the first 48 h, exendin-4 signi... See full list on link.springer.com For measurement of hormone release, five islets were cultured in 1 ml of medium in triplicate for 48 h as previously described and the concentrations of human IAPP and insulin in the culture medium measured. For content, five islets in triplicate were extracted with acid-ethanol . Human IAPP and insulin concentrations were determined by ELISA (Hum... See full list on link.springer.com Total RNA was isolated from 25 islets per condition (High Pure RNA isolation kit; Roche Applied Science, Indianapolis, IN, USA) and reverse-transcribed (High Capacity cDNA Archive kit; Applied Biosystems, Foster City, CA, USA). mRNA expression of human IAPP and Insulin II gene was measured in triplicate using the TaqMan system (ABI Prism 7000; Appl... See full list on link.springer.com Total protein was extracted from at least 200 islets per condition (Cell Lysis kit; Bio-Rad Laboratories, Hercules, CA). Islet protein (35 g islet protein per sample) was separated by SDS-PAGE, transferred to PVDF membrane and then probed with a pAKT antibody (1:500; Cell Signaling, Danvers, MA, USA) or total AKT antibody (1:500; Cell Signaling), ... See full list on link.springer.com Data are expressed as mean SEM and were compared by analysis of variance with least significant difference post-hoc analysis, or by KruskalWallis and MannWhitney U non-parametric tests if not normally distributed. A value of p< 0.05 was considered statistically significant. See full list on link.springer.com Increasing human IAPP release with exendin-4 or KCl increased amyloid deposition. However, while KCl further increased beta cell apoptosis and beta cell loss, exendin-4 did not. Conversely, decreasing human IAPP release with diazoxide or somatostatin limited amyloid formation and its toxic effects. IAPP release is necessary for islet amyloid formation and its toxic effects, and use of insulin secretagogues to treat type 2 diabetes may result in increased isletAmyloidogenesis and beta cell death, but the AKT-associated anti-apoptotic effects of GLP-1 receptor agonists such as exendin-4 may limit the toxic effects of increased iseloid formation. Aims/hypothesisIn type 2 diabetes ... Exendin-4 increases islet amyloid deposition but offsets the resultant beta cell toxicity in human islet amyloid polypeptide transgenic mouse islets July 2011 Diabetologia 54 (7):1756-65 Treatment with exendin-4 was associated with an increase in AKT phosphorylation compared with control and KCl-treated islets. IAPP release is necessary for islet amyloid formation and its toxic effects. Thus, use of insulin secretagogues to treat type 2 diabetes may result in increased islet amyloidogenesis and beta cell death. Exendin-4 increases islet amyloid deposition but offsets the resultant beta cell toxicity in human islet amyloid polypeptide transgenic mouse islets.

Exendin-4 increases islet amyloid deposition but offsets the resultant beta cell toxicity in human islet amyloid polypeptide transgenic mouse islets July 2011 Diabetologia 54 (7):1756-65

Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies. Pancreatic alpha cell mass in European subjects with type 2 diabetes. Exendin-4 increases islet amyloid deposition but...

In rat islets cultured with exendin-4, HIF-1 mRNA and protein expression were significantly enhanced. ATP content was increased in exendin-4-treated INS-1E cells under hypoxic conditions.