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No description available.

Transglutaminase 2 (TG2) is a functionally and structurally complex ubiquitous protein. TG2 has Ca2+-dependent transamidating activity, can bind and hydrolyze ATP/GTP, function as a G-protein in intracellular signaling, and has reported kinase activity. TG2 knockout mice are observed to have impaired glucose-stimulated insulin secretion (GSIS). Three naturally occurring mutations, including Met330Arg, Ile331Asn, and Asn333Ser, have been reported in the TG2 protein and observed to be related with maturity onset diabetes of the young (MODY). Overexpression of the naturally occurring Myc-tag mutants in INS-1E cells generated a loss in GSIS compared to wild type-TG2 overexpression. Each mutant was shown to have diminished transamidation and kinase activities, along with altered GTP-binding which was responsive to glucose stimulation. Naturally occurring mutations in TG2 impact the transamidation, kinase, and GTP-binding functions of TG2. The GTP-binding function of TG2 has a significant impact on GSIS from pancreatic beta cells in addition to its transamidating activity.

Understanding how the insulin gene is regulated is essential to developing new treatments for diabetes mellitus. The aim of this study was to characterise, in detail, the effect of stress, glucose and insulin on three protein kinases, p38, JNK and PKB in pancreatic β cells. p38 was found to be active in both INS-1 and MIN-6 cells in response to the stress inducing agents anisomycin, UV and sodium arsenite. Physiologically high levels of glucose failed to result in p38 activation. Experiments were undertaken to characterise the effect of p38 overexpression on the activity of the rat insulin promoter. p38 overexpression resulted in a 10 fold increase in rat insulin promoter activity under conditions of high glucose however cells treated with the stress inducing agents UV and sodium arsenite showed a decrease in rat insulin promoter activity relative to controls. JNK was also detected in INS-1 and MIN-6 cells. JNK activity was increased by the cellular stresses of UV, sodium arsenite and anisomycin, but not by physiologically high levels of glucose. Overexpression of the transcription factor c-Jun inhibited the rat insulin gene promoter's response to glucose but overexpression of JNK had no effect. Furthermore JNK and c-Jun overexpression did not alter the size of the transcription factor PDX-1. PKB activity was found to be high in untreated INS-1 cells and could only be activated using significant quantities of insulin over a long time period. PKB overexpression in INS-1 cells led to a 10-20 fold increase in the activity of the rat insulin<span lang=EN-GB style='font-family:Arial'> promoter under conditions of both low and high glucose. Further experiments were undertaken to evaluate the use of an adenoviral system to overexpress PKB in β cells in a controlled manner. Finally, a pilot study was undertaken to examine the effect of overexpressing Ngn3, a transcription factor essential to the development of the pancreas in rat liver cells.

No description available.

Transglutaminase 2 (TG2) is a functionally and structurally complex ubiquitous protein. TG2 has Ca2+-dependent transamidating activity, can bind and hydrolyze ATP/GTP, function as a G-protein in intracellular signaling, and has reported kinase activity. TG2 knockout mice are observed to have impaired glucose-stimulated insulin secretion (GSIS). Three naturally occurring mutations, including Met330Arg, Ile331Asn, and Asn333Ser, have been reported in the TG2 protein and observed to be related with maturity onset diabetes of the young (MODY). Overexpression of the naturally occurring Myc-tag mutants in INS-1E cells generated a loss in GSIS compared to wild type-TG2 overexpression. Each mutant was shown to have diminished transamidation and kinase activities, along with altered GTP-binding which was responsive to glucose stimulation. Naturally occurring mutations in TG2 impact the transamidation, kinase, and GTP-binding functions of TG2. The GTP-binding function of TG2 has a significant impact on GSIS from pancreatic beta cells in addition to its transamidating activity.

Many of the symptoms of zinc deficiency and diabetes are the same, and are related to increased inflammation. Zinc supplementation may improve immunity and glycemic control, and reduce inflammation. The purpose of this study was to determine if marginal zinc deficiency (MZD) worsens and zinc supplementation (ZS) improves diabetes and immune parameters in Zucker diabetic fatty (ZDF) rats. Male ZDF rats were fed MZD (4 mg Zn/kg diet), zinc control ([ZC], 30 mg Zn/kg diet), or ZS (300 mg Zn/kg diet) diet, and lean ZDF rats fed ZC diet for 8 weeks. Parameters of diabetes, inflammation, and immune cell proportions and function were assessed. Results showed that MZD may exacerbate diabetes but had little effect on the immune parameters, while ZS had little effect on diabetes but may worsen immune function. Overall, it is the balance between zinc deficiency and toxicity that is necessary for optimal health improvements.

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No description available.