Reduced dihydroxyacetone sensitivity and normal sensitivity to glyceraldehyde and oxidizing agent of ATP-sensitive K+ channels of pancreatic beta cells in NIDDM rats.
The inhibition of ATP-sensitive K+(KATP) channels in pancreatic beta cells is a key step of insulin secretion induced by glucose. Glucose-induced insulin secretion from the beta cells is selectively impaired in patients with noninsulin-dependent diabetes mellitus (NIDDM) and in animal models of it. In order to clarify the site of this abnormal glucose response, we studied the effects of insulin secretagogues and sulfhydryl oxidizing agent, 2,2'-dithio-bis (5-nitropyridine) (DTBNP), on KATP channels in single beta cells of neonatally streptozotocin-induced NIDDM rats. We used the patch-clamp technique in cell-attached mode (Vpipette = 0 mV). The inhibitory response to glucose of KATP channels was lacking in NIDDM rats, indicating reduced sensitivity to glucose of the channels. Glyceraldehyde (2-5 mM) in the diabetic beta cells elicited the same KATP channel inhibition as that obtained in controls. In contrast, dihydroxyacetone (DHA, 2-10 mM) sensitivity of KATP channels was significantly reduced in the beta cells of NIDDM rats. KATP channels in the diabetic beta cells were rapidly inhibited by 50 microM DTBNP, just as in the normal beta cells, suggesting that KATP channel function was normal. This indicates that one of the sites responsible for impaired glucose-induced insulin secretion in the pancreatic beta cells of NIDDM rats is located in the glycerol phosphate shuttle.
Song
D K
DK
Department of Physiology, Keimyung University School of Medicine, Dankook University, Korea.
Park
W K
WK
Bae
J H
JH
Park
M K
MK
Kim
S J
SJ
Ho
W K
WK
Earm
Y E
YE
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004098:Dihydroxyacetone / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D005985:Glyceraldehyde / Q000494:pharmacology; D005994:Glycerophosphates / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D005994:Glycerophosphates; D016877:Oxidants; D015221:Potassium Channels; D011725:Pyridines; D013439:Sulfhydryl Reagents; C011801:2,2'-dithiobis(5-nitropyridine); D005985:Glyceraldehyde; D000255:Adenosine Triphosphate; D005947:Glucose; D004098:Dihydroxyacetone