Glucose-dependent and -independent electrical activity in islets of Langerhans of Psammomys obesus, an animal model of nutritionally induced obesity and diabetes

Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

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Development of macroangiopathy in sand rats (Psammomys obesus), an animal model of non-insulin-dependent diabetes mellitus: Effect of gliclazide

The American Journal of Medicine ◽

10.1016/0002-9343(91)90419-x ◽

1991 ◽

Vol 90 (6) ◽

pp. S55-S61 ◽

Cited By ~ 11

Author(s):

Georges Marquié ◽

Peter Hadjiisky ◽

Olivier Arnaud ◽

Jacques Duhault

Keyword(s):

Diabetes Mellitus ◽

Animal Model ◽

Insulin Dependent Diabetes Mellitus ◽

Insulin Dependent Diabetes ◽

Dependent Diabetes Mellitus ◽

Psammomys Obesus ◽

Insulin Dependent

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Dissociation by methylamine of insulin release from glucose-induced electrical activity in isolated mouse islets of Langerhans

Metabolism ◽

10.1016/0026-0495(85)90157-x ◽

1985 ◽

Vol 34 (12) ◽

pp. 1122-1127 ◽

Cited By ~ 5

Author(s):

P. Lebrun ◽

I. Atwater ◽

L.M. Rosario ◽

A. Herchuelz ◽

W.J. Malaisse

Keyword(s):

Electrical Activity ◽

Insulin Release ◽

Islets Of Langerhans ◽

Mouse Islets

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Leptin and Its Relation to Obesity and Insulin in the SHR/N-corpulent Rat, A Model of Type II Diabetes Mellitus

International Journal of Experimental Diabetes Research ◽

10.1155/edr.2001.217 ◽

2001 ◽

Vol 2 (3) ◽

pp. 217-223 ◽

Cited By ~ 16

Author(s):

Manuel T. Velasquez ◽

Sam J. Bhathena ◽

Carl T. Hansen

Keyword(s):

Animal Model ◽

Plasma Glucose ◽

Type Ii Diabetes ◽

Plasma Insulin ◽

Entire Group ◽

Type Ii ◽

Fasting Plasma ◽

Obesity And Diabetes ◽

Obese Rats ◽

Plasma Leptin

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of theobgene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p<0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r=0.73, p<0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r=0.54, p<0.05). There was also a significant positive.correlation between plasma leptin and plasma insulin in the entire group (r=0.70, p<0.01). However, this relationship was significant only for lean rats but not for obese rats (r=0.59, p<0.05 for lean rats, and r=0.23, p=NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r=0.75, p<0.05), total cholesterol (r=0.63, p<0.05), and triglyceride (r=0.67, p <0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome.

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