Lack of Wdr13 Gene in Mice Leads to Enhanced Pancreatic Beta Cell Proliferation, Hyperinsulinemia and Mild Obesity

WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes

A critical review of mathematical models and data used in diabetology

The literature dealing with mathematical modelling for diabetes is abundant. During the last decades, a variety of models have been devoted to different aspects of diabetes, including glucose and insulin dynamics, management and complications prevention, cost and cost-effectiveness of strategies and epidemiology of diabetes in general. Several reviews are published regularly on mathematical models used for specific aspects of diabetes. In the present paper we propose a global overview of mathematical models dealing with many aspects of diabetes and using various tools. The review includes, side by side, models which are simple and/or comprehensive; deterministic and/or stochastic; continuous and/or discrete; using ordinary differential equations, partial differential equations, optimal control theory, integral equations, matrix analysis and computer algorithms

The effect of physiologic hyperinsulinemia during an oral glucose tolerance test on the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) in healthy young adults born with low and with normal birth weight

Several data support that adrenal hyperandrogenism affects women with low birth weight (LBW). We also found an association between serum dehydroepiandrosterone (DHEA) and fasting insulin levels. The aim of our study was to detect the acute effects of reactive hyperinsulinemia during oral glucose tolerance test (OGTT) on DHEA(S) levels in LBW men and women. Fifty three men and 47 women (of those, 37 men and 33 women were LBW) were enrolled. DHEA, DHEAS, and insulin levels were measured before and during OGTT. Cortisol was also measured. DHEA/cortisol ratio during OGTT was calculated to analyze the acute effect of hyperinsulinemia on DHEA levels. During OGTT, DHEA and cortisol levels decreased in each individual, independently of gender and birth weight. Serum DHEAS decreased to a minor (but significant) extent only in LBW women (p<0.05). The rate of DHEA/cortisol increased in both gender, independently of birth weight. The increase of the rate of DHEA/cortisol during OGTT was associated with maximal insulin response (r = 0.45, p<0.05) and with the insulin(AUC) (r = 0.48, p<0.05) in women. Our results suggest that reactive hyperinsulinemia during OGTT might activate the androgen pathway of adrenal cortex including DHEA production. Therefore acute hyperinsulinemia might counterbalance to some extent the diurnal decrease of DHEA during OGTT