Insulin Receptor Deficiency in Genetic and Acquired Obesity

Ah, Soli; Kahn, C. Ronald; Dm, Neville; Roth, Jesse

doi:10.1172/jci108155

Cited by 254 publications

(106 citation statements)

References 34 publications

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“…In addition to the fact that starch and sucrose are metabolically not identical [20], MacDonald and Turner [16] suggested, that the "rate of presentation" of a carbohydrate, including the speed of chewing, swallowing and digestion, influencing the extent of postprandial hyperglycaemia, might be the determining factor in inducing the increased activity of lipogenic enzymes, leading to enhanced fat deposits. The additional fat tissue might effectively contribute to the elevated secretion of insulin in sucrose fed rats by way of a reduction of the number of insulin receptors, as usually found and recently described in acquired obesity [25]. The overall magnitude of insulin response to the same intravenous glycaemic stimulus is markedly con-ditioned by the antecedent carbohydrate intake.…”

Section: Discussionmentioning

confidence: 70%

Insulin secretion and biosynthesis in sucrose fed rats

et al. 1976

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Summary. Long term feeding of a sucrose rich diet to rats is accompanied by a decreased glucose assimilation rate, despite high plasma insulin levels. Hyperinsulinism is at least partially based on a relative obesity, with increased amounts of abdominal-and retroperitoneal fat tissue, but unchanged total body weight compared to starch fed controls. The " secretory pattern of insulin release was studied following glucose, arginine, fructose and sulfonylurea administration in the isolated perfused pancreas of sucrose and isocaloric starch fed rats. In addition, isolated islets of Langerhans were used to demonstrate the effects of glucose on insulin secretion and the incorporation of H-3 leucine into the proinsulin and insulin fraction of islet proteins. Following 11 mM glucose, the dynamics of insulin release in the isolated perfused pancreas of sucrose fed rats is characterized by a markedly elevated, late plateau-like response, usually seen only at higher glucose concentrations. Hyperinsulinism, as compared to starch fed controls, can also be demonstrated following arginine and the sulfonylurea HB-4t9, whereas fructose has no effect in the presence of low glucose concentrations. During incubation of the pancreatic islets, the hyperinsulinism in sucrose-, compared to starch fed rats, is more pronounced at 11 mM glucose than at 5.5 mM glucose. The incorporation of H-3 leucine into the proinsulininsulin fraction of islet proteins in sucrose compared to starch fed rats, however, is significantly greater with glucose 5.5 mM than at high glucose level. In sucrose fed rats, secretion and biosynthesis of insulin thus appear to be elevated but closely linked only at physiological glucose concentration. * This work was supported by Deutsche Forschungsgemeinschaft SFB 87, Endokrinotogie, Ulm.Key words: Sucrose, increased body fat, isolated perfused pancreas, dynamics of insulin secretion, hyperinsulinism, insulin biosynthesis, isolated islets of Langerhans.High sucrose concentration in the diet leads to a diabetic glucose tolerance in rats [4], despite elevated levels of glucose-induced insulin secretion [12]. This effect was correlated by some authors with the preferential rate of liver metabolism of fructose compared to glucose [24]. Others, however, considered this as a consequence of the fast postprandial blood sugar rise, resulting in a massive impact of glucose on the carbohydrate regulating mechanisms of the body, in particular the B-ceU [3]. Since delayed but increased insulin release and slow glucose assimilation rate are known to be frequently determined by diet composition [8] and obesity [1], we decided to analyze to what extent changes in the diet, in particular a high sucrose content, might affect the body fat content and the quantity of insulin release in rats.As there is no strict correlation between insulin secretion and biosynthesis [22], further studies, aimed at revealing the connection between both specific processes of the B-cell in sucrose induced diabetic metabolism in rats, were carried out. Materi...

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Section: Discussionmentioning

confidence: 70%

Insulin secretion and biosynthesis in sucrose fed rats

et al. 1976

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“…the insulin receptor; Soll, Kahn, Neville & Roth, 1975) or drugs with their membrane receptors (e.g. the 3-adrenoceptor; Lefkowitz, Limbird, Mukherjee & Caron, 1976).…”

Section: Discussionmentioning

confidence: 99%

DOWN‐REGULATION OF THE SODIUM PUMP FOLLOWING CHRONIC EXPOSURE OF HeLa CELLS AND CHICK EMBRYO HEART CELLS TO OUABAIN

Aiton

Lamb

Ogden

1981

British J Pharmacology

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HeLa cells and primary cultures of embryonic chick heart cells were grown in medium containing low concentrations of ouabain for 24 h. Compared with normal cells, cells grown in ouabain have fewer free sodium pump sites, an increased intracellular sodium concentration and a decreased intracellular potassium concentration. The cells are able to maintain their intracellular ion contents because the remaining pump sites have an increased turnover rate. When cells that have been chronically exposed to ouabain are returned to normal growth medium, the sodium pump site numbers increase; the recovery process begins within 6 to 8 h and is complete within 24 h. Recovery of pump site numbers is primarily dependent upon de novo protein synthesis since the protein synthesis inhibitor, cycloheximide, prevents recovery.

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“…Decrease in insulin binding to receptors may certainly play a role in insulin resistance in animal and human obesity [24,25,26,27,28]. Evidence is, however, given both in animals [29] and in humans [30,31] that decrease in the number of insulin receptors is secondary to hyperinsulinism and is not the primary cause of insulin resistance in obesity.…”

Section: Discussionmentioning

confidence: 99%

Glucose storage and oxidation in different degrees of human obesity measured by continuous indirect calorimetry

Felber¹,

Meyer²,

Curchod

et al. 1981

Diabetologia

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Summary. Glucose disposal of a 100 g glucose load has been determined in 26 obese compared with 10 non-obese subjects by means of a new application of continuous indirect calorimetry. The obese subjects were divided into 4 groups, according to their degree of glucose intolerance and their insulin response to the glucose load. Through this division it appeared that subjects with no glucose intolerance were moderately obese while the groups with glucose intolerance showed a higher degree of obesity, glucose intolerance increasing with age. The 10 obese subjects with no glucose intolerance (group A) presented values for glucosedisposal similar to those of the control subjects. The 4 obese subjects with impaired glucose tolerance. (group B) showed no significant changes in glucose storage and in basal oxidation, but a significant decrease in oxidation in response to the load (11 _+ 2g vs 19 _-2 lg in the control group, p <0.02). The 6 obese subjects with overt diabetes and elevated insulin response to the glucose load (group C) showed a significant decrease in glucose storage (34 _.+ 6 g vs 63 --_ I g, p < 0.001) but not in oxidation. The 6 obese subjects With overt diabetes and decreased insulin response (group D) showed a significant decrease in glucose storage (25 +4 g vs 63 -+ 1 g, p < 0.001) and oxidation (12 +__ i g, vs 19 + 1 g, p < 0.005). These observations show that in obese diabetics, glucose intolerance results primarily from decreased glucose storage and to a lesser extent from a decrease in glucose oxidation.

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Insulin Receptor Deficiency in Genetic and Acquired Obesity

Cited by 254 publications

References 34 publications

Insulin secretion and biosynthesis in sucrose fed rats

Insulin secretion and biosynthesis in sucrose fed rats

DOWN‐REGULATION OF THE SODIUM PUMP FOLLOWING CHRONIC EXPOSURE OF HeLa CELLS AND CHICK EMBRYO HEART CELLS TO OUABAIN

Glucose storage and oxidation in different degrees of human obesity measured by continuous indirect calorimetry

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