The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity

Salans, Lester B.; Knittle, Jerome L.; Hirsch, Jules

doi:10.1172/jci105705

Cited by 560 publications

(310 citation statements)

References 34 publications

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“…In agreement with the suggestion of several investigators [9,10] the metabolic parameters studied are expressed on a cellular basis. Mean cell diameter was determined on cells isolated with collagenase (Type I, Sigma Chemical Co., St. Louis, Mo.)…”

Section: Methodssupporting

confidence: 83%

“…Thus, it seems valid to conclude that the prolonged exposure to these concentrations of insulin may influence the cellular responsiveness to the hormone. This finding may be relevant for the fact that large fat cells from subjects with obesity and hyperinsulinemia [27,28] exhibit a diminished responsiveness to insulin in vitro [10] as well as in vivo [39]. At least for the adipose tissue it may well be, as also suggested by Grey and Kipnis [40], that the diminished acute effect of insulin represents an adaptive phenomenon which is secondary to the hyperinsulinemia.…”

Section: Discussionmentioning

confidence: 67%

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Human adipose tissue in culture V. Studies on the metabolic effects of insulin

1976

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Summary.Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradrenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in the cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G6PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PFK, were not increased. Most probably, *Part of these data were presented at the First International Congress on Obesity in London, England on 9-11 October, 1974. then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.

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Section: Methodssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 67%

Human adipose tissue in culture V. Studies on the metabolic effects of insulin

1976

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“…In the sandrat there is an initial increase and a subsequent fall of the serum insulin level attributed to pancreatic exhaustion [15]. Obesity decreases the insulin sensitivity of adipose tissue also in Wellesley hybrid mice [6] and human subjects [18]. Preliminary studies denoted that hyperinsulinemia occurs also in obese gerbils.…”

Section: Discussionmentioning

confidence: 99%

Ob�sit� et hyperplasie des �lots du pancr�as chez la gerbille mongolienne

Boquist

1972

Diabetologia

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Summary. In a colony of Mongolian gerbils maintained on a standard laboratory diet, occasional obese animals were found. Obesity developed in animals of both sexes and was either transitory or permanent. The mean fasting blood glucose level in non-obese and obese gerbils was 83 and 105 rag/100 ml, respectively. Glucosuria and hyperglycemia were found only in a few obese animals, whereas the glucose tolerance was decreased in most obese gerbils. --The endocrine pancreas of the obese animals was morphologically either normal or more often hyperplastic, sometimes with the appearance of adenomatous islets. The fl-eells possessed prominent Golgi complex and endoplasmic reticulum, and sparse granulation. Large, granule-poor cells and mitotic figures were seen in the islets. Degenerative changes occurred in the fl-cells of diabetic animals. --It is suggested that the maintenance of the gerbils under laboratory conditions with free access to laboratory diet plays a majo r role in the development of obesity and that the endocrine pancreas of these animals has a good capacity for hyperplasia that often is sufficient to maintain normo-glycemia in obese animals, although the glucose tolerance is decreased. Obdsit@ et hyperplasie des ilots du panerdas chez la gerbille mongolienneRdsumd. Dans un 61evage de gerbilles mongoliennes soumises ~ un r@gime standard de laboratoire ont dr@ parfois trouvds des animaux ob@ses. L~ se dgveloppait chez les animaux des deux sexes et 6tait tantSt transitoire, tant6t permanente. Le taux moyen de glucose du sang, ~ jefin, ehez les animaux non ob@ses et ob~-ses 6tait respectivement de 83 et 105 mg/100 ml. La glyeosurie et l'hyperglycdmie n'dtaient trouvdes que ehez peu d'animaux ob6ses, tandis que la toldrance au glucose 6tait rdduite ehez la plupart des animaux ob@ses. --Le pancrdas endocrine des animaux ob@ses dtait, morphologiquement, normal ou plus souvent hyperplasique avec parfois l'apparition d'ilots adgnomateux. Les eellules /~ poss@daient un eomplexe de Golgi et un rdticulum endoplasmique pro@minents et une granulation faible. De grosses eellules pauvres en granules et des figures mitotiques se montraient dans les ilots. Des changements d@gdndratifs se produisaient dans les cellules fl des animaux diab6tiques. --On sugg~re que le maintien des animaux darts les conditions de laboratoire avec libre acc@s au r@gime de laboratoire joue un r61e prddominant darts le d@veloppement de I'ob@sit@ et que le pancr@as endocrine de ces animaux a une excellente eapaeit6 d'hyperplasie qu! suffit souvent ~ maintenir la normoglycdmie ehez les ammaux ob@ses, malgr6 la r6duction de la tol6rance au glucose. ~]bergewieht und Hyperplasie der Pankreasinseln bei der mongolischen RennmausZusammenfassung.

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“…Research in obese humans has shown that as adipose cells enlarge, their responsiveness to insulin decreases (Salans et al, 1968). Work in sheep has demonstrated that as they become fatter, fat cells enlarge and adipose vascularity decreases (Gregory et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Whole body insulin responsiveness is higher in beef steers selected for increased muscling

McGilchrist

Pethick

Bonny

et al. 2011

Animal

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The aim of this experiment was to evaluate the impact of selection for greater muscling on whole body insulin responsiveness in cattle, as reflected by greater uptake of glucose in response to constant insulin infusion and greater glucose disappearance following an intravenous glucose tolerance test. This study used 18-month-old steers from an Angus herd visually assessed and selected for divergence in muscling over 15 years. Eleven high-muscled (High), 10 low-muscled (Low) and 3 high-muscled steers, which were heterozygous for a myostatin polymorphism (High Het ), were infused with insulin using the hyperinsulineamiceuglyceamic clamp technique. Insulin was constantly infused at two levels, 0.6 mIU/kg per min and 6.0 mIU/kg per min. Glucose was concurrently infused to maintain euglyceamia and the steady state glucose infusion rate (SSGIR) indicated insulin responsiveness. An intravenous glucose tolerance test was also administered at 200 mg/kg live weight. Sixteen blood samples were collected from each animal between 230 and 130 min relative to the administration of intravenous glucose, plasma glucose and insulin concentration was determined in order to analyse insulin secretion and glucose disappearance. Insulin-like growth factor-1 (IGF-1) was also measured in basal plasma samples. At the low insulin infusion rate of 0.6 mU/kg per min, the SSGIR was 73% higher for the High muscling genotype animals when compared to the Low (P , 0.05). At the high insulin infusion rate of 6.0 mU/kg per min, these differences were proportionately less with the High and the High Het genotypes having only 27% and 34% higher SSGIR (P , 0.05) than the Low-muscled genotype. The High-muscled cattle also had 30% higher plasma IGF-1 concentrations compared to the Low-muscled cattle. There was no effect of muscling genotype on basal insulin or basal glucose concentrations, glucose disappearance or insulin secretion following an intravenous glucose tolerance test. The increased whole body insulin responsiveness in combination with higher IGF-1 concentrations in the High-muscled steers is likely to initiate a greater level of protein synthesis, which may partially explain the increased muscle accretion in these animals.

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The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity

Cited by 560 publications

References 34 publications

Human adipose tissue in culture V. Studies on the metabolic effects of insulin

Human adipose tissue in culture V. Studies on the metabolic effects of insulin

Ob�sit� et hyperplasie des �lots du pancr�as chez la gerbille mongolienne

Whole body insulin responsiveness is higher in beef steers selected for increased muscling

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