-Duque F Elghazi L Weiss A Gould A Chang-Chen KJ Gambello MJ Bernal-Mirzrachi E 2008 Disruption of Tsc2 in pancreatic beta cellsinduces beta cell mass expansion and improved glucose tolerance in a TORC1-dependentmanner . PNAS 105 9250 – 9255
Afreen Idris Shariff, Sohail Syed, Rebecca A Shelby, Jeremy Force, Jeffrey Melson Clarke, David D’Alessio and Leonor Corsino
R Buettner, K G Parhofer, M Woenckhaus, C E Wrede, L A Kunz-Schughart, J Schölmerich and L C Bollheimer
assayed in the different diet groups by performing insulin tolerance tests (Fig. 2 ). Glucose levels in SC rats dropped from 5.0 ± 0.3 mmol/l to minimally 3.7 ± 0.8 mmol/l at 30 min after intraperitoneal insulin injection. The insulin-induced glucose
O. Bchini, M. Mehtali and R. Lathe
Glucose tolerance was studied in transgenic mice (SJL × C57BL/6) expressing human GH under the control of a housekeeping promoter. Parental SJL mice were found to harbour a dominant allele, termed here gli d, determining glucose intolerance in pure-bred animals and in Fl hybrids with glucose-tolerant C57BL/6 mice. Blood glucose levels in transgenic SJL × C57BL/6 hybrid mice were well controlled following glucose challenge, whereas non-transgenic hybrids failed to control their glucose adequately. Pancreatic morphology was normal in all animals. In confirmation of a physiological role for GH in glucose regulation, GH-deficient lit/lit mice were pathologically sensitive to glucose.
Li Hu, Fengli He, Meifeng Huang, Meihua Peng, Zhiguang Zhou, Feng Liu and Yan-Shan Dai
, Kusminski et al . 2016 , Deng et al . 2017 ). A number of studies have demonstrated that inhibiting macrophage infiltration in white AT can improve glucose tolerance in the context of obese mice ( Osborn & Olefsky 2012 , Aouadi et al . 2013 ). Also
Karen Oliva, Gillian Barker, Clyde Riley, Mark J Bailey, Michael Permezel, Gregory E Rice and Martha Lappas
(Heidelberg, Australia) and Ethics Committee and informed consent was obtained from all participating subjects. Human placenta was obtained from lean and obese pregnant women with normal glucose tolerance at the time of term Caesarean section before the onset
J. U. Weaver, G. A. Hitman and P. G. Kopelman
Obesity is likely to be a multifactorial disease with an important genetic component. Animal models of genetic and experimentally induced obesity suggest that glucocorticoid receptor (GR) activity plays a role in the aetiology and maintenance of the obese state. Glucocorticoid activity appears to be essential for the development of hyperinsulinaemia and subsequent fat deposition. In humans, glucocorticoid excess is associated with central fat distribution. We have therefore investigated the restriction fragment length polymorphisms of the human GR gene locus (GRL) and have sought associations of specific alleles with anthropometric measurements and indices of insulin secretion and resistance in obesity.
Fifty-six extremely obese, unrelated, nondiabetic premenopausal British Caucasian females and 43 age-matched, normal weight controls were studied. The obese subjects were characterized by fat distribution (waist to hip ratio), insulin secretion and insulin resistance (fasting insulin (FI)), an index of insulin resistance (HOMA), stimulated insulin secretion during an oral glucose tolerance test and insulin-mediated glucose disposal, steady-state plasma glucose). A BclI polymorphism (fragments of 4·5 and 2·3 kb) demonstrated significant association with indices of glucose metabolism in obesity; those subjects homozygous for the 4·5 kb fragment had elevated FI (Pc=0·012) and HOMA (Pc=0·012) values. The genotypic and allelic frequencies of the GRL BclI polymorphism were otherwise similar in obese and normal weight subjects. We postulate that the GRL BclI polymorphism may directly affect GR gene expression, or be in linkage disequilibrium with a possible mutation within one of three exons of the GR gene, and thereby modulate GR transcriptional activity on target genes involved in glucose and insulin homeostasis.
R Perfetti, H Hui, K Chamie, S Binder, M Seibert, J McLenithan, K Silver and JD Walston
The Arg64 beta(3)-adrenergic receptor (beta(3)AR) variant is associated with an earlier age of onset of diabetes and lower levels of insulin secretion in humans. The aims of this study were to investigate whether beta(3)AR is expressed by islet cells, if receptor binding affects insulin secretion and, finally, if the beta(3)AR Arg64 variant induces abnormal insulin secretory activity. Human pancreas extracts were subjected to RT-PCR, Western blotting and immunostaining analyses. DNA sequencing and Western blotting demonstrated that the beta(3)AR gene is transcribed and translated in the human pancreas; immunostaining showed that it is expressed by the islets of Langerhans. Cultured rat beta-cells responded to human beta(3)AR agonists in a dose- and time-dependent manner. Transfection of cultured rat beta-cells with the wild-type human beta(3)AR produced an increased baseline and ligand-dependent insulin secretion compared with parental cells. On the other hand, cells transfected with the Arg64 variant of the beta(3)AR secreted less insulin, both spontaneously and after exposure to human beta(3)AR agonists. Furthermore, while transfection with the wild-type beta(3)AR preserved the glucose-dependent secretion of insulin, expression of the variant receptor rendered the host cells significantly less responsive to glucose. In summary, cells express the beta(3)AR, and its activation contributes to the regulation of insulin secretion. These findings may help explain the low levels of insulin secretion in response to an i.v. glucose tolerance test observed in humans carrying the Arg64 polymorphism.
Jiazhong Sun, Yancheng Xu, Haohua Deng, Suxin Sun, Zhe Dai and Yanlei Sun
spikes in the pathogenesis of diabetic complications . Diabetic Medicine 15 188 – 193 . Ceriello A 2004 Impaired glucose tolerance and cardiovascular disease: the possible role of post-prandial hyperglycemia . American Heart Journal 147
Anthony L Albiston, Mauricio Cacador, Puspha Sinnayah, Peta Burns and Siew Yeen Chai
et al . 2008 ). Glucose handling after an oral glucose challenge The effect of IRAP inhibitor HFI-419 on whole animal glucose handling was evaluated after an oral glucose tolerance test (OGTT) in male Sprague–Dawley rats. Twelve rats were
Y Y Liu, W Jia, I E Wanke, D A Muruve, H P Xiao and N C W Wong
complied with guidelines at University of Calgary. Intraperitoneal glucose tolerance test Mice fasted >6 h were injected i.p. with 2 g/kg glucose ( Davalli et al . 1995 ) and glucose monitored 15 or 30 min up to 120 min. Serum assays Serum was separated