BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.

Blood Glucose↗

PubMedDate not supplied

Studies on the morphologic and metabolic changes of human fat cells maintained in culture.

Specimens of human adipose tissue were maintained in vitro for one week and cell size as well as metabolic rates determined before and after the culture period. Large fat cells from obese donors decreased towards 'normal' cell size while this was not the case for cells from non-obese donors. This decrease was probably due to the increased lipolysis found while glucose incorporation was unchanged. Analogous to the findings with obese subjects placed on a weight-reducing regimen, the present data show that when large fat cells are removed from their anabolic, hyperinsulinic environment, 'normalization' in cell size occurs.

Adipose Tissue↗

PubMedDate not supplied

A study of different methods for the assay of lipoprotein lipase activity in human adipose tissue.

A method for the assay of lipoprotein lipase activity (LPLA) in heparin eluates of needle biopsies of adipose tissue is presented. A serum activated phosphatidestabilized emulsion of labelled triolein has been used as substrate. This method and a previously described method using heparin eluates as enzyme source and a commercial triglyceride emulsion, Ediol, as substrate, showed a high degree of correlation (correlation coefficient = 0.94) when parallel determinations were performed on biopsies from 16 subjects. Further, the Ediol method similarly correlated well with a method for LPLA assay, previously described by Nilsson-Ehle and Belfrage, on acetone-ether extracts of adipose tissue (correlation coefficient = 0.88; 19 subjects).

Adipose Tissue↗

PubMedDate not supplied

Altered recognition of hypoglycaemic symptoms in type I diabetes during intensified control with continuous subcutaneous insulin infusion.

The effect of intensified metabolic control obtained with continuous subcutaneous insulin infusion (CSII) on the frequency and symptoms of hypoglycaemia was studied in type I diabetic patients. The reproducibility of the questionnaire used to evaluate the hypoglycaemic symptoms was verified in a control group receiving unchanged conventional insulin therapy for 2 months. Metabolic control was significantly improved during CSII (HbA1c 6.8 +/- 0.4% versus 8.7 +/- 0.7%, normal range up to 5.4%) in all patients while no change was seen in the control group. The results of frequent self glucose monitoring showed that the incidence of low glucose levels (below 3.5 mmol/l) increased about threefold in the CSII group. Awareness of hypoglycaemia was clearly changed during CSII with less pronounced adrenergic symptoms while no alterations were found in the group with unchanged metabolic control. These results emphasize the importance of regular self glucose monitoring during CSII and of informing the patients that their hypoglycaemic symptoms may change during intensified control.

Adult↗

PubMedDate not supplied

Insulin resistance in fat cells from insulin-treated type I diabetic individuals.

Fat biopsies from the lower abdominal wall were obtained from 13 insulin-treated type I diabetic subjects and from 12 age-, weight-, and sex-matched control subjects. Insulin binding and the antilipolytic effect of insulin were studied. Insulin binding was significantly reduced in the diabetic subjects (34% reduction at tracer binding, P less than 0.05) due to a decreased number of binding sites. In agreement with this, the dose-response curve for the antilipolytic effect of insulin was shifted to the right in the diabetic subjects. Furthermore, the maximal antilipolytic effect of insulin was also reduced (64%, P less than 0.05). Thus, fat cells from conventionally treated type I diabetic individuals are resistant to insulin. This resistance is due to a combination of a decreased number of insulin binding sites and an unspecified intracellular (postreceptor) defect involving the antilipolytic effect of insulin. These findings are in accord with recent in vivo studies showing that type I diabetic patients are also resistant to the stimulating effect of insulin on glucose disposal.

Adipose Tissue↗

PubMedDate not supplied