Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes
Article Abstract:
Non-insulin-dependent diabetes mellitus (NIDDM), the most common cause of hyperglycemia (elevated levels of glucose, or sugar, in the blood), results when the pancreatic beta cells cannot manufacture sufficient insulin for the body's needs. This occurs when the body's cells develop insulin resistance, or reduced ability to respond to insulin, and the beta cells cannot compensate for this increased resistance. The beta cells in NIDDM patients are able to secrete insulin in response to stimuli other than glucose, however; thus, a defect in insulin secretion specific to the pathways that involve glucose is likely. This hypothesis was explored in a rodent model of NIDDM, the Zucker diabetic fatty rat. Results from studying the beta cells and metabolic processes of these animals showed that, indeed, the beta cells of very hyperglycemic rats did not secrete insulin when stimulated with glucose. Closer investigation revealed a defect in the glucose uptake system (in high Km glucose transport), possibly impairing the cells' ability to distinguish high blood glucose levels from normal ones. Histological methods were used to evaluate GLUT-2 (the protein that transports glucose across the cell membrane) and the RNA (ribonucleic acid) responsible for making GLUT-2; results showed that the levels of these substances were dramatically reduced in NIDDM rats. Quantitative studies showed that animals with fewer than 60 percent of their beta cells staining positive for GLUT-2 (the method by which the presence of GLUT-2 was inferred) had the greatest hyperglycemia and lacked an insulin response to glucose. Thus, the pathology in NIDDM appears to begin with reduced expression of GLUT-2, resulting in impaired transport of glucose across the cell membrane. Insulin secretion is then impaired, and the animal (or person) becomes hyperglycemic. Further elucidation of these mechanisms could lead to the development of new therapeutic approaches. (Consumer Summary produced by Reliance Medical Information, Inc.)
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1990
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Does leptin contribute to diabetes caused by obesity?
Article Abstract:
Research indicates that secretion of the satiety-inducing peptide leptin by adipose tissues may be a way that obesity causes insulin resistance and non-insulin-dependent diabetes mellitus. However, the results raise some questions, and further research is needed.
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1996
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Cyclic ADP-ribose in beta cells
Article Abstract:
A series of experiments comparing the Ca2+-mobilizing effects of the two second messengers in beta cells found no Ca2+ release following the addition of cyclic ADP-ribose. These results contradict those of Shin Takasawa. Possible explanations are discussed.
Publication Name: Science
Subject: Science and technology
ISSN: 0036-8075
Year: 1993
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