High fat diet modulation of glucose sensing in the beta-cell.
Type 2 diabetes is primarily associated with beta-cell failure, insulin resistance and elevated hepatic glucose production. The islet beta-cell is specialized for the synthesis, storage and secretion of insulin. Beta-cell failure is characterized by the inability of the beta-cell to secrete sufficient insulin in response to glucose, which ultimately results in hyperglycemia- the clinical hallmark of Type 2 diabetes. Impairment in glucose sensing contributes to beta-cell dysfunction. The facilitative glucose transporter, GLUT-2, and glucose phosphorylating enzyme, glucokinase, are key for glucose sensing of the pancreatic beta-cell, the initial event in the pathway for glucose-stimulated insulin secretion. There is an increase in dietary fat intake, particularly saturated fat, in both the developing and Westernized world, which predisposes individuals to become obese and to potentially develop insulin resistance, beta-cell dysfunction and Type 2 diabetes. A high fat diet is known to reduce both GLUT-2 and glucokinase expression thereby impairing glucose-stimulated insulin secretion. Furthermore, a high fat diet and specific free fatty acids, induces oxidative stress and apoptosis which reduces beta-cell mass and compromises beta-cell function. Glucose sensing is the initial event of glucose-stimulated insulin secretion therefore it is imperative to maintain adequate expression levels of GLUT-2 and GK for ensuring normal beta-cell function. The development of pharmaceutical agents that improve glucose-stimulated insulin secretion may replenish expression of these glucose sensing genes after their attenuation by high fat feeding.
Cerf
Marlon E
ME
Diabetes Discovery Platform, South African Medical Research Council, Tygerberg, South Africa. marlon.cerf@mrc.ac.za
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects*; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D009004:Monosaccharide Transport Proteins