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

Abstract

1. The effects of glucose, glucose 6-phosphate, and l-glycerol 3-phosphate on the incorporation of [1-14C]palmitate into neutral lipid have been studied in homogenates of adipose tissue obtained from adult diabetics and control patients. In the diabetic, glucose, glucose 6-phosphate and l-glycerol 3-phosphate supported incorporation of 19, 27 and 62% of total counts respectively; whereas in paired non-diabetic controls the respective values were 78, 80 and 84%. 2. Confirmation of these results were provided by finding slower rates of conversion of [U-14C]glucose into phosphate esters in diabetic adipose tissue compared to paired non-diabetic controls. Rates were improved but not restored to normal by treatment of diabetic patients with insulin. 3. These results could not be explained on the basis of differences in isotope dilution in precursor pools or to the presence of raised levels of free fatty acids in diabetic tissue. 4. A group of latent diabetics showed a pattern of substrate utilization more like fully developed diabetes than non-diabetic controls. Rates of glucose phosphorylation were slower in latent diabetics than in paired controls. 5. Studies were also performed with homogenates of adipose tissue prepared from patients with Cushing's disease, obesity and pregnancy, these groups being predisposed to develop adult diabetes. 6. In Cushing's disease (eight patients) glucose, glucose 6-phosphate and l-glycerol 3-phosphate supported incorporation of 9 ± 1 (13), 19·2 ± 3·9 (10) and 23·2 ± 3·3 (9)% of total counts at 2 hr respectively; whereas in paired controls respective values were 19·7 ± 3·4 (10), 25·7 ± 2·8 (10) and 26·4 ± 2·9 (10)%. Support for these results was provided by finding slower rates (by about 50%) of conversion of [U-14C]glucose into phosphate esters in tissue from Cushing's disease compared to paired controls. 7. Ten obese patients with no clinical evidence of diabetes showed a pattern of substrate utilization more like diabetic adipose tissue; whereas another eight obese patients resembled their non-obese controls. 8. Adipose tissue from six pregnant patients (over 10 weeks) showed a diabetic pattern of substrate utilization; and confirmation was provided by rates of [U-14C]glucose conversion into phosphate esters (as counts × 10 min−1 mg protein−1 hr−1) of 929 ± 75 (5) in pregnancy versus 1386 ± 198 (5) in paired controls.