title: Plasma leptin concentrations do not appear to decrease insulin-mediated glucose disposal or glucose-stimulated insulin secretion in women with normal glucose tolerance.
abstract: The aim of this study was to test the hypothesis that plasma leptin concentrations contributed to the pathophysiology of NIDDM by decreasing both insulin-mediated glucose disposal and glucose-stimulated insulin secretion. The study was performed in 60 women with normal oral glucose tolerance. Differences in insulin-mediated glucose disposal were determined by comparing the steady-state plasma glucose (SSPG) concentrations attained at the end of a 180-min constant infusion of somatostatin, glucose, and insulin, while comparisons of glucose-stimulated insulin secretion were based on the incremental increase in insulin concentration 30 min after an oral glucose challenge (deltaIns) as compared with the fasting value. The results showed that the higher the fasting plasma leptin concentration, the greater the degree of insulin resistance (r = 0.47, P < 0.01). Furthermore, multiple regression analysis indicated that the relationship between leptin and SSPG was independent of age and degree of obesity as estimated by BMI. However, since the total integrated plasma insulin response was highly correlated with both SSPG (r = 0.80, P < 0.001) and leptin (r = 0.55, P < 0.01), multiple regression analysis was repeated, adding total insulin response to the model. When this was done, the significant relationship between leptin and SSPG disappeared, whereas both BMI (P < 0.03) and insulin response (P < 0.001) were correlated with SSPG. A significant relationship between leptin and deltaIns was seen, but it was a positive one (r = 0.31, P < 0.02), not a negative one as would be expected if circulating levels of leptin inhibited glucose-stimulated insulin secretion. Furthermore, multiple regression analysis could only confirm an independent relationship between deltaIns and SSPG, but not between deltaIns and leptin. The results of these studies do not support the view that circulating leptin has a primary effect on either insulin action or secretion in normal female volunteers. It seems more likely that chronic hyperinsulinemia in insulin-resistant individuals acts to increase adipose tissue leptin synthesis and secretion, leading to higher ambient leptin concentrations.
authors.affiliation: Stanford University School of Medicine, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Carantoni
authors.forename: F
authors.initials: F
authors.lastname: Abbasi
authors.forename: S
authors.initials: S
authors.lastname: Azhar
authors.forename: Y D
authors.initials: YD
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Klebanov
authors.forename: P W
authors.initials: PW
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Warmerdam
authors.forename: G M
authors.initials: GM
authors.lastname: Reaven
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D020738:Leptin; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D012044:Regression Analysis; D013004:Somatostatin
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011506:Proteins; D013004:Somatostatin