Abnormalities in glucose-stimulated insulin release, 45Ca uptake, and 86Rb efflux in diabetic Chinese hamster islets.
We loaded islets from normal and diabetic Chinese hamsters with 86Rb (an analogue for K+) and measured 86Rb efflux during stimulation with 20 mM D-glucose. Genetically diabetic Chinese hamsters were selected from a subline (L) known for subnormal pancreatic insulin release and excessive pancreatic glucagon release in vitro. 86Rb accumulation in 1 mM glucose was normal in the diabetic islets. Similar to the pattern of 86Rb efflux previously seen from normal rat and mouse islets, 20 mM glucose suppressed 86Rb efflux within 1-2 min, and efflux remained suppressed until return to 1 mM glucose in both normal and diabetic hamster islets. After the first 2 min of 20 mM glucose, suppression of 86Rb efflux was somewhat greater in the diabetic hamster islets than in the normals. In addition, glucose-stimulated insulin release and 45Ca uptake were significantly reduced in the diabetic islets. Therefore, in the diabetic hamster islets, there is at least no impairment in the initial suppression of 86Rb efflux by glucose. This suggests that the diabetic beta-cells recognize glucose and carry out the initial steps in the stimulus-secretion coupling sequence normally. The later, excessive suppression of 86Rb efflux may be due to impaired Ca2+-induced changes in 86Rb efflux, suggesting that defective regulation of intracellular Ca2+ activity, rather than defective regulation of K+ permeability, may lead to the impaired insulin secretion.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011868:Radioisotopes; D012413:Rubidium / Q000378:metabolism*
D002132:Calcium Radioisotopes; D007328:Insulin; D011868:Radioisotopes; D005947:Glucose; D012413:Rubidium; D002118:Calcium