Antiobesity effect of diazoxide in obese Zucker rats

Ramin Alemzadeh, William Jacobs, Pisit Pitukcheewanont

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Hyperinsulinism and insulin resistance are characteristic findings in obese subjects. Obesity in both humans and experimental animals is associated with a reduced number of insulin receptors and a decreased insulin-mediated glucose disposal, whereas sensitivity to insulin's antilipolytic action is unaltered. To evaluate the antiobesity effect of diazoxide (DZ), an inhibitor of glucose-stimulated insulin release, 7-week-old Zucker obese and lean rats were studied. Obese and lean rats were grouped into DZ-treated (150 mg/kg/d) and control (C) groups. DZ-treated obese rats consumed similar amounts of calories per kilogram body weight (BW) compared with C obese animals, but gained less weight (P < .01). Postabsorptive plasma free fatty acids (FFA), cholesterol, and triglycerides were significantly higher in obese versus lean animals (P < .01), DZ treatment reduced plasma triglyceride levels in obese animals (P < .001), but had no significant affect on FFA or cholesterol concentrations. Plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests (GTTs) were significantly lower in DZ obese versus C obese rats (P < .01) despite a decrease in plasma insulin concentrations in DZ-treated animals (P < .01). In contrast, DZ lean rats developed glucose intolerance (P < .05). Sensitivity and responsiveness to the antilipolytic effect of insulin in isolated adipocytes were significantly decreased in DZ obese as compared with C obese rats (P < .01). Moreover, adipocyte specific insulin receptor binding was increased in both DZ lean and DZ obese animals (P < .01). This was accompanied by increased basal and insulin-stimulated glucose transport in both genotypes (P < .01). In conclusion, DZ increased insulin receptor binding and glucose transport while decreasing hyperinsulinemia and insulin sensitivity to the antilipolytic action of insulin. This combined effect resulted in improved glucose tolerance and a decrease in weight gain in obese rats, implying that pharmacologic modification of the disturbed insulin metabolism of obesity may be therapeutically beneficial.

Original languageEnglish (US)
Pages (from-to)334-341
Number of pages8
JournalMetabolism: clinical and experimental
Volume45
Issue number3
DOIs
StatePublished - Jan 1 1996

Fingerprint

Diazoxide
Zucker Rats
Insulin
Glucose
Insulin Receptor
Insulin Resistance
Hyperinsulinism
Nonesterified Fatty Acids
Adipocytes
Triglycerides
Obesity
Cholesterol
Dilatation and Curettage
Glucose Intolerance
Glucose Tolerance Test
Weight Gain
Genotype
Body Weight

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Antiobesity effect of diazoxide in obese Zucker rats. / Alemzadeh, Ramin; Jacobs, William; Pitukcheewanont, Pisit.

In: Metabolism: clinical and experimental, Vol. 45, No. 3, 01.01.1996, p. 334-341.

Research output: Contribution to journalArticle

Alemzadeh, Ramin ; Jacobs, William ; Pitukcheewanont, Pisit. / Antiobesity effect of diazoxide in obese Zucker rats. In: Metabolism: clinical and experimental. 1996 ; Vol. 45, No. 3. pp. 334-341.
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