Verapamil reverses glucose intolerance in preexisting chronic renal failure: studies on mechanisms.
Glucose-induced insulin secretion is impaired in chronic renal failure (CRF), and this abnormality is due to the elevation of cytosolic calcium [Ca2+]i and other derangements in pancreatic islet metabolism. Verapamil given to rats from day 1 of CRF prevented the rise in [Ca2+]i of islets and the impairment in insulin secretion. However, it is not known whether verapamil can reverse the abnormalities of islet function and metabolism in animals with preexisting renal failure. Such a documentation has important clinical implications for the treatment of carbohydrate intolerance in patients with CRF. The present study examined this question. After 6 weeks of CRF, rats were randomized into two subgroups and maintained for additional 6 weeks. One subgroup received intraperitoneal injections of verapamil (0.1 micrograms/kg body weight twice daily) and the other received vehicle only. At the time of randomization, there were no significant differences between the two subgroups in their body weight, plasma levels of calcium, phosphorus and creatinine, serum parathyroid hormone and creatinine clearance. Similarly, at the time of sacrifice (12 weeks), there were no significant differences in these parameters except for a modestly lower plasma level of creatinine and modestly higher creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Thanakitcharu
P
P
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Fadda
G Z
GZ
Hajjar
S M
SM
Levi
E
E
Stojceva-Taneva
O
O
Massry
S G
SG
D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000032:analysis; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase