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Glucokinase activity in isolated islets from obese fa/fa Zucker rats.

ABSTRACT: Glucokinase (EC 2.7.1.2) activity of B-cells was measured in extracted pancreatic islets isolated from lean and obese fa/fa Zucker rats and maintained in primary culture overnight. Formation of [14C]glucose phosphoric esters from D-[U-14C]glucose was measured in the presence of unlabelled glucose from 0.05 to 0.50 mM for hexokinase (EC 2.7.1.1) activity, and 8.0-16.0 mM unlabelled glucose for glucokinase activity. Eadie-Hofstee analysis revealed that hexokinase kinetic parameters (Vmax and Km) for [14C]glucose phosphoric ester formation were similar in lean- and fa/fa-rat islets. For glucokinase, there was no difference in Vmax. between phenotypes. A non-significant tendency to increased sensitivity to glucose was noted in the fa/fa-rat islets (P = 0.13). In lean-rat islets, the glucokinase inhibitor mannoheptulose (3 mM) decreased Vmax. by 80% and increased the apparent Km from 3.3 +/- 0.7 mM to 12.2 +/- 2.0 mM (P < 0.05). There was no difference in Km or Vmax. in mannoheptulose-treated versus control islets from fa/fa rats. This lack of effect was consistent with reported effects of mannoheptulose on insulin secretion from fa/fa-rat islets [Chan, MacPhail and Mitton (1993) Can. J. Physiol. Pharmacol. 71, 34-39]. The data from glucose and mannoheptulose experiments support the hypothesis that glucokinase function is altered in fa/fa Zucker rats and may contribute to fasting hyperinsulinaemia in vivo in these animals.

SUBMITTER: Chan CB

PROVIDER: S-EPMC1134612 | biostudies-other | 1993 Nov

REPOSITORIES: biostudies-other

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Transcription profiling of hepatocyes from Zucker fa/fa obese rats vs controls

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The effects of corticosterone, cold exposure and overfeeding with sucrose on brown adipose tissue of obese Zucker rats (fa/fa).

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Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.

Project description:BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

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Alterations in G-protein expression and the hormonal regulation of adenylate cyclase in the adipocytes of obese (fa/fa) Zucker rats.

Project description:Attenuated maximal activations by forskolin, Mn+. NaF or guanosine 5'-[gamma-thio]triphosphate (GTP[S]) were noted for adenylate cyclase activity in adipocytes from obese (fa/fa) Zucker rats compared with their lean (Fa/Fa) littermates. GTP[S] achieved half-maximal activation of adenylate cyclase at some 10-fold lower concentrations in membranes from lean animals compared with those from obese. Levels of the 42 and 45 kDa forms of Gs were some 40-50% lower in membranes from obese animals, and levels of Gi-1 and Gi-3 were some 62-65% lower. No differences in levels of Gi-2 alpha-subunits or G-protein beta-subunits were observed. Gi function, as assessed by inhibiting forskolin-stimulated adenylate cyclase, achieved by prostaglandin E1, nicotinate and phenylisopropyladenosine, was similar in membranes from both lean and obese animals. Levels of beta-adrenoceptors were some 50% lower in membranes from obese animals. It is suggested that the attenuated activation of adenylate cyclase by stimulatory ligands in membranes from obese animals may be caused by decreases in both Gs and receptors, and that this may contribute to the attenuated lipolytic response seen in adipocytes from such animals.

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