The development of obesity, hyperinsulinemia, and hyperglycemia in ob/ob mice

Dubuc, Paul U.

doi:10.1016/0026-0495(76)90109-8

Cited by 155 publications

(98 citation statements)

References 20 publications

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“…(Figure 1) as expected. 5,6 This is analogous to the effect observed in obese subjects, which show elevated hepatic TAG content and a high degree of steatosis. 8,9 There was a concomitant increase in the activities of both DGATs by very similar factors (2.5-fold, see Figure 2) such that the ratio of DGAT II to DGAT I activity remained constant.…”

Section: Resultssupporting

confidence: 68%

“…More recently, the cDNAs of genes coding for two separate DGATs have been cloned and sequenced. 3,4 In the present study, the activities of both DGATs I and II in lean Ob=?, and ob=ob null mice, which have steatotic livers and are hypertriglyceridaemic, 5,6 were investigated in order to study whether the relative activities of the two DGATs are affected by the altered hepatic metabolic profile of these animals.…”

Section: Introductionmentioning

confidence: 99%

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Activities of overt and latent diacylglycerol acyltransferases (DGATs I and II) in liver microsomes of ob/ob mice

Waterman

Zammit

2002

Int J Obes

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The effect of the ob=ob mutation on microsomal overt and latent acyl CoA:diacylglycerol acyl transferase activities (DGATs I and II) in liver microsomes of mice was investigated. Overt and latent hepatic DGAT activities for 16-week-old lean Ob=? mice were 0.42 AE 0.14 and 1.57 AE 0.04 mmol=mg=min, respectively. For ob=ob mice DGAT I and II activities were 1.17 AE 0.28 and 3.09 AE 0.78 mmol=mg=min, respectively. The hepatic triacylglycerol (TAG) concentration of 16-week-old mice was increased three-fold in ob=ob mice relative to those in lean controls. The data suggest that the increased rate of hepatic TAG secretion and intracellular accumulation in ob=ob mice is accompanied by parallel increases in the activities of both DGATs.

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Section: Resultssupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Activities of overt and latent diacylglycerol acyltransferases (DGATs I and II) in liver microsomes of ob/ob mice

Waterman

Zammit

2002

Int J Obes

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“…In support of this, rodent models of leptin deficiency are characterised by insulin resistance and diabetes [8,9], and leptin treatment lowers blood glucose and insulin levels [10] independent of changes in food intake and body weight [11]. Moreover, leptin administration in both rodents [12,13] and humans [14] ameliorates the severe insulin resistance and diabetes phenotype characteristic of other models of leptin deficiency that are not associated with obesity, such as lipodystrophy, a condition characterised by loss of adipose tissue owing to mutations that impair adipogenesis [15].…”

Section: Leptin Regulation Of Glucose Metabolismmentioning

confidence: 91%

The role of leptin in diabetes: metabolic effects

2016

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While it is well established that the adiposity hormone leptin plays a key role in the regulation of energy homeostasis, growing evidence suggests that leptin is also critical for glycaemic control. In this review we examine the role of the brain in the glucose-lowering actions of leptin and the potential mediators responsible for driving hyperglycaemia in states of uncontrolled insulin-deficient diabetes (uDM). These considerations highlight the possibility of targeting leptin-sensitive pathways as a therapeutic option for the treatment of diabetes. This review summa-

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“…One interpretation is that b 3 -AR expression is being repressed by additional components of the ob/ob syndrome not corrected by RU-486. An obvious candidate is insulin because hyperinsulinemia occurs immediately after weaning in ob/ob mice, 1 and insulin was shown to decrease mRNA and decrease function of the b 3 -AR in 3T3-F442A adipocytes. 48 Thus, the failure of RU-486 to fully correct hyperinsulinemia in ob/ob mice may have prevented complete restoration of b 3 -AR expression.…”

Section: Ru-486 Ameliorates Diabetesmentioning

confidence: 99%

“…During this same period, adipose tissue from ob/ob mice undergoes a ®ve-fold expansion in size compared to lean littermates. 1 Of particular interest is the observation that adipose tissue from ob/ob mice is resistant to stimulation of lipolysis by b-adrenergic agonists. 2±4 We have recently presented evidence that this defect results from decreased expression of b 1 -and b 3 -adrenergic receptor subtypes and their cognate G protein, G s a, 5,6 but the underlying cause for dysregulation of these genes has not been established.…”

Section: Introductionmentioning

confidence: 99%

RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient β-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice

et al. 1997

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OBJECTIVE: To investigate the role of hypercorticism in the development of compromised b-adrenergic signalling in adipocytes of mature C57BL/6J-ob/ob mice. DESIGN AND EXPERIMENTAL UNITS: Mature male ob/ob mice and their lean littermates were treated with vehicle or the speci®c glucocorticoid receptor (GR) antagonist, RU-486 (30 mg/kg bw/d) for 21 d. MEASUREMENTS: Blood glucose, serum insulin, adipocyte Glut-4 expression, adipocyte G s a expression, adenylylcyclase activation by b-adrenergic receptor (b-AR) agonists in adipocyte membranes and mRNA levels for b 1 -, b 2 -and b 3 -adrenergic receptor subtypes in adipocytes. RESULTS: RU-486 reduced blood glucose levels in ob/ob mice to levels that were not different from lean mice. RU-486 also reduced serum insulin by approximately 50% in ob/ob mice, but failed to restore depressed G s a or GLUT-4 expression in adipocytes of ob/ob mice. RU-486 produced a two-fold increase in b 3 -AR mRNA in ob/ob mice and a small but signi®cant improvement in isoprenaline-mediated adenylylcyclase activation. CONCLUSIONS: The present results indicate that glucocorticoid antagonism ameliorates diabetic symptoms of the mature ob/ob mouse, but does not lessen their obesity or fully reverse de®cient expression and function of components of the adipocyte b-adrenergic signalling cascade.

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The development of obesity, hyperinsulinemia, and hyperglycemia in ob/ob mice

Cited by 155 publications

References 20 publications

Activities of overt and latent diacylglycerol acyltransferases (DGATs I and II) in liver microsomes of ob/ob mice

Activities of overt and latent diacylglycerol acyltransferases (DGATs I and II) in liver microsomes of ob/ob mice

The role of leptin in diabetes: metabolic effects

RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient β-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice

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