Hyperglycemia contributes to impaired insulin response in GK rat islets.
Insulin secretion and glucose metabolism were compared in pancreatic islets from type 2 diabetic GK rats treated with phlorizin or vehicle. Treatment of control and GK rats with phlorizin for 30 days did not affect body weight, islet glucose utilization, or islet glucose oxidation. In phlorizin-treated GK rats, glucose-induced insulin release was about twofold higher at 11.0 and 16.7 mmol/l glucose compared with vehicle, treated GK rats, whereas phlorizin had no effect on control Wistar rats. However, also in phlorizin-treated GK rats, the amount of insulin released by the islets was significantly less than that from control rats (5.29+/-0.33 vs. 7.50+/-1.31 pmol x min(-1) islet(-1) at 16.7 mmol/l glucose; P<0.001). Islet glucose-6-phosphatase activity was significantly higher in GK rats than in control rats; phlorizin treatment significantly decreased this activity. These findings demonstrate that hyperglycemia per se constitutes an important factor for impaired insulin release in GK rats. Correction of hyperglycemia normalizes islet glucose-6-phosphatase activity, which may be an underlying factor for the partial improvement of glucose-induced insulin release.
Department of Molecular Medicine, Rolf Lufts Centrum for Diabetes Research, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
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Ling
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Hong-Lie
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Ostenson
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Efendic
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Khan
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007328:Insulin; D010695:Phlorhizin; D005952:Glucose-6-Phosphatase; D005947:Glucose