Role of basal insulin in maintenance of intracellular glucose metabolic pathways in non-insulin-dependent diabetes mellitus.
Impairments of both basal and insulin-stimulated oxidative (Gox) and nonoxidative (Nox) glucose metabolism are documented to exist in non-insulin-dependent diabetes mellitus (NIDDM). Although these defects have been well characterized during insulin stimulation, little is known about the effects of basal insulin or its deficiency on intracellular glucose metabolism in NIDDM. To determine the physiological significance of basal insulin in the maintenance of glucose metabolism in NIDDM, we studied nine subjects with NIDDM in the basal and insulin-deficient state produced by 3 hours of somatostatin (SRIF) infusion (0.08 pmol/kg/min). Glucose turnover rates were quantified by [3-3H]glucose turnover, and substrate oxidation was assessed by a combination of indirect calorimetry and urinary nitrogen measurements. Skeletal muscle glycogen synthase (GS) and pyruvate dehydrogenase (PDH) activities were also measured in the basal state and during SRIF infusion. Basal glucose levels were maintained during SRIF infusion by exogenous glucose infusion (12.5 +/- 0.9 mmol/L in the basal state v 12.8 +/- 0.8 during SRIF infusion, P = NS). During the last hour of SRIF infusion, plasma C-peptide levels declined by 88% from 0.73 +/- 0.11 to 0.09 +/- 0.02 nmol/L (P < .001), and serum insulin concentrations were undetectable (< 14 pmol/L). During insulinopenic conditions, rates of glucose uptake (GU) were decreased by 12% from basal level of 2.26 +/- 0.13 to 1.99 +/- 0.12 mg/kg/min (P < .05), and were entirely accounted for by reduced rates of Gox (1.01 +/- 0.10 to 0.65 +/- 0.14 mg/kg/min, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of California-San Diego, La Jolla.
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Suh
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Song
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Murata
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Joyce
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Ditzler
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Henry
D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D013004:Somatostatin; D006006:Glycogen Synthase; D005947:Glucose