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Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM

  • Chapter
New Concepts in the Pathogenesis of NIDDM

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 334))

Abstract

Non-insulin-dependent diabetes mellitus (NIDDM) is a hereditary, chronic disease which is characterized by hyperglycemia. In most patients with manifest NIDDM, signs of hormonal dysbalance as well as insulin resistance are evident (1,2). Of the hormonal disturbances, impaired glucose-stimulated insulin response from the B-cells stands out as the most important defect (1,3). However, altered A- and D-cell secretion of glucagon and somatostatin, respectively, may also contribute to the diabetic state. Thus, the glucagon response to amino acids given i.v. and mixed meal is exaggerated and the suppressi-bility of glucagon release by glucose administered orally or i.v. is reduced (4,5). As in case of insulin release, glucose-induced somatostatin release is impaired or abolished (6). Since normalization of blood glucose levels by insulin infusion restored somatostatin response in NIDDM patients (7), the defect in D-cell function appears secondary to hyperglycemia and/or hypoinsulinemia. The mechanisms behind the altered A-cell response in NIDDM are more complex. Thus, after normalization of glycemia in artificial pancreas normal glucagon responses were found when patients were given intravenous arginine (8) and glucose (9). Conversely, even after normalization of glucose control in artificial pancreas, a mixed meal induced an exaggerated glucagon response, while oral glucose failed to suppress glucagon levels (7). Interestingly, in patients with insulin-dependent diabetes mellitus treatment with artificial pancreas normalized glucagon responses irrespective whether glucose or amino acids were given i.v. or orally (10, 11).

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Authors and Affiliations

  1. Department of Endocrinology and Rolf Lufts Center for Diabetes Research, Karolinska Hospital and Institute, S-104 01, Stockholm, Sweden

    Claes-Göran Östenson, Akhtar Khan & Suad Efendic

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  1. Claes-Göran Östenson
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  2. Akhtar Khan
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  3. Suad Efendic
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Editors and Affiliations

  1. Karolinska Hospital, Stockholm, Sweden

    Claes Göran Östenson  & Suad Efendić  & 

  2. University of Toronto, Toronto, Ontario, Canada

    Mladen Vranic

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Östenson, CG., Khan, A., Efendic, S. (1993). Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM. In: Östenson, C.G., Efendić, S., Vranic, M. (eds) New Concepts in the Pathogenesis of NIDDM. Advances in Experimental Medicine and Biology, vol 334. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2910-1_1

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  • DOI: https://doi.org/10.1007/978-1-4615-2910-1_1

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