The Effect of Insulin on Human Adipose Tissue

Abstract

The effects of insulin on glucose transport and dissimilation have been studied in the rat fat pad and in human omentum. Intracellular glucose could not be demonstrated in the non-diabetic rat fat pad, with or without insulin. Slices of omentum, obtained during surgery from diabetic and non-diabetic patients, were incubated in a bicarbonate medium with a glucose concentration of 5.6 mM. Omentum from non-diabetic patients had intracellular glucose while diabetic tissue had none. Diabetic tissue had a significantly lower glucose uptake. In both, insulin stimulated glucose uptake in inverse relation to the basal uptake; but for comparable basal uptakes, the response to insulin was decreased in diabetic tissue. Glucose phosphorylation in omental tissue from non-diabetic humans had an apparent Km of 1.10 m M and a Vmax of 1.44 mg/g hour.Insulin (0.1 units/ml), bovine or human serum albumin, or a combination of insulin and bovine albumin, each increased glucose utilization by slices of non-diabetic omentum without affecting the intracellular glucose content or the free fatty acid content. In omental homogenates (cell-free), insulin and bovine serum albumin each increased the glucose utilization. In the presence of albumin, insulin increased the utilization only after the addition of glucose-6-phosphate dehydrogenase and phosphohexose isomerase in amounts sufficient to establish that hexokinase was rate-limiting for glucose utilization.It is concluded that (A) in diabetic human omentum and in normal rat fat pad, transport is rate-limiting in glucose utilization; (B) insulin and albumin each stimulate both transport and phosphorylation in human omentum; (C) in human diabetes, the glucose transport process of omentum has a decreased basal rate and a decreased responsiveness to insulin.

A Defect of Glucose Utilization in Adipose Tissue of Adult Diabetics and in Some Conditions Which May Predispose to Diabetes

“…Field, Johnson & Herring (1961) noticed a similar tendency in isolated human adipose tissue, in which a group of four non-diabetic patients consumed 2.16&0.13 mg glucose/g tissue, compared to four obese diabetics utilizing 1.69 +O-12 mg glucose/g tissue. Kahlenberg & Kalant (1964) employing a similar experimental design, confirmed these results and showed that omental tissue from eight diabetics took up less glucose from the incubation medium than their non-diabetic controls whether in the presence or absence of insulin. They concluded that impaired glucose transport was responsible for this effect in diabetic tissue.…”

Comparative Effects of Insulin on Adipose Tissue Segments and Isolated Fat Cells of Rat and Man*

“…Previous reports describe an insulin effect on glucose metabolism by human adipose tissue only with pharmacological doses of either 100 mU/ml (25,26,(4)(5)(6) or 10 mU/ml of insulin (7). Since completion of our work, Owen et al (27) …”

“…In light of the variable metabolic behavior of adipose tissue obtained from the different species of laboratory animals (2, 3), one might question the rele-vance of studies performed in the rat to human adipose tissue metabolism. As a matter of fact, recent data obtained in man seem to indicate that, contrary to the rat, human adipose tissue in vitro is insensitive to physiological doses of insulin (4)(5)(6)(7). This hypothesis carries important implications, as it would shift the emphasis from adipose tissue to the liver as 'the major site of fat synthesis.…”

“…This hypothesis carries important implications, as it would shift the emphasis from adipose tissue to the liver as 'the major site of fat synthesis. However, it has been recognized that the poor response of human adipose tissue to insulin may be related to a variety of factors such as dietary preparation of the patient, effects of anesthesia, and methods of collecting the tissue (4,5). Apart from these considerations, rat epididymal fat differs from human subcutaneous fat in its anatomical configuration.…”

Metabolismo del tessuto adiposo umano incubato in vitro I - effetto dell'insulina sul consumo di glucosio e produzione di CO2 in diverse condizioni sperimentali

“…KAHLEMBERG (8) ha studiato il comportamento del tessuto adiposo umano dell'omento e dai suoi risultati ha tratto la conclusione che nel normale il fattore limitante il metabolismo glicidico è rappresentato dalla fosforilazione del glucosio; mentre ne/ diabetico, nel quale il consumo di glucosio da parte del tessuto si dimostra inferiore alla norma, il fattore limitante sarebbe rappresentato dal passaggio dell'esoso attraverso la membrana cellulare.…”