Genetically obese rats with (SHR/N-cp) and without diabetes (LA/N-cp) share abnormal islet responses to glucose.
To assess the effect of hyperglycemia on the function of islets obtained from obese rats, the behavior of isolated islets from LA/N-corpulent (nondiabetic obese) and SHR/N-corpulent (diabetic obese) male rats was examined and compared. Islets from both genetic models showed a left-shifted glucose dose-response curve for insulin release (concentrations for half-maximal release, 5 to 6 mmol/L v 12 to 13 mmol/L in LA/N lean littermates and 3 mmol/L v 10 mmol/L in lean SHR/N). When insulin release was expressed per unit islet volume, the fourfold to fivefold enlarged islets from both obese diabetic and obese nondiabetic rats showed decreased insulin secretory response in high (16.5 to 28 mmol/L) glucose concentrations, although the decrease was more severe in the diabetic rats. Glucose-stimulated insulin release by islets from both models was relatively resistant to inhibition by 1.2 mmol/L mannoheptulose (eg, 82% +/- 3% inhibition in LA/N lean v 16% +/- 8% in LA/N obese), although nearly complete inhibition was observed with 16 mmol/L mannoheptulose (96% v 85%, NS). Islets of obese diabetic rats were also resistant to the calcium-channel blocker, verapamil, suggesting an abnormal pathway of stimulus-secretion coupling for glucose. Glucose oxidation to carbon dioxide was increased in both obese models at all glucose concentrations when expressed per islet. In data expressed per unit volume, the larger islets from the obese-nondiabetic rats showed a left-shifted dose-response curve with an unchanged maximum rate of glucose oxidation at high (16.5 mmol/L) glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Timmers
K I
KI
Diabetes Research Laboratory, Veterans Administration Medical Center, Washington, DC.
Voyles
N R
NR
Recant
L
L
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D002469:Cell Separation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D007515:Islets of Langerhans / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics*; D011922:Rats, Mutant Strains; D014700:Verapamil / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D008356:Mannoheptulose; D014700:Verapamil; D005947:Glucose