Effect of Obesity on Insulin Sensitivity of Human Adipose Tissue

Abstract

Subcutaneous abdominal adipose tissue was removed from six normal weight patients (118–184 lb.) at laparotomy and six obese subjects (280–533 lb.) under local anesthesia and incubated in vitro. Glucose-C-14 incorporation into CO2, total lipids and glycogen were measured. Although insulin (10 mU./ml.) stimulated CO2 production from glucose in all twelve subjects (p < .001), the average increase was only 26.6 per cent (5.3 to 50.8). Radioactive glucose incorporation into total lipids was increased by insulin in eight of twelve subjects (average rise = 21.9 per cent; range, −45.5 to 107.1 per cent), but this failed to achieve significance. This small insulin effect on human adipose tissue reflects the experience of others. On the other hand, insulin-stimulated glycogen synthesis proved to be the most sensitive indicator of hormonal activity (mean rise = 231.9 per cent; range, 66.2 to 562.2 per cent). There was no significant difference in basal or insulin-stimulated glucose incorporation into CO2, total lipids or glycogen between the obese and normal weight subjects. The insulin effect on glycogen synthesis could not be correlated with either weight index or body fat in these twelve subjects. Basal conversion of glucose to CO2 was significantly correlated with these two measures of obesity (r = 0.6, p < .05). These data corroborate two other reports that obesity is associated with increased basal glucose metabolism by human adipose tissue in vitro. However, they fail to substantiate the postulate that adipose tissue of the obese is insensitive in insulin. These results and the fact that only approximately 5 per cent of basal or. insulin-stimulated glucose turnover in vivo involves adipose tissue suggest that insensitivity of the muscle mass and/or a circulating insulin antagonist should be more important in the insulin antagonism of obesity.

Impaired fasting glucose with or without impaired glucose tolerance: progressive or parallel states of prediabetes?

“…Close anthropometric matching between groups implies a central role for obesity, rather than glucose dysregulation, as dictating peripheral insulin action. Indeed, previous work has noted far greater differences in peripheral insulin action when obese NGT vs. lean NGT is compared (10,20) than when obese NGT vs. prediabetes is compared (36,46). In summary, no differences were noted in peripheral insulin action between IFG, IFG/IGT, and NGT in the current study.…”

“…More surprising was the lack of notable decrement in peripheral insulin action in either IFG or IFG/IGT vs. NGT in the current study and may relate to the close anthropometric matching between groups. Previous work has implicated obesity (10,20), rather than glucose dysregulation (36,46), in the decline of peripheral insulin action characteristic of diabetes. Alternatively, small numbers in the groups may have obscured differences, as Tripathy et al (41) noted 19% lower peripheral insulin sensitivity comparing overweight people with IFG/IGT (n ϭ 29) to those with NGT (n ϭ 216).…”

Effect of Protracted Intermittent Fasting on the Activities of Enzymes Involved in Energy Metabolism, and on the Concentrations of Glycogen, Protein and DNA in Skeletal Muscle of Obese Women

“…Although the regulatory mechanism which controls the glycogen content of muscle is not fully known, the work of Hultman and Nilson (18), Roch-Norlund et al (28,29) and Bergstrom et al (2) emphasises the basic regulatory impor tance of insulin and glucose, the glycogen content being influenced also in a significant way by exercise and diet. With regard to this work, the lower glyco gen values we recorded in obese women could be associated with a lower biologi cal action of insulin in peripheral tissues (6,25), a problem which requires further investigation.…”

Adipose cell size and glucose tolerance in obese children and effects of diet

“…Brook and Llcyd Discussion The work of Davidson (1972) indicates that the adipose tissue of obese subjects may not be insensitive to insulin, and suggests that insensitivity of the muscle mass and/or a circulating insulin antagonist could be more important in the insulin resistance of obesity. The present results likewise do not support the concept that adipose cell size is the most important cause of the hyperinsulinism of obesity.…”