Effect of insulin on glycerol production in obese adolescents

Abstract

Impaired stimulation of glucose metabolism and reduced suppression of lipolytic activity have both been suggested as important defects related to the insulin resistance of adolescent obesity. To further explore the relationship between these abnormalities, we studied seven obese [body mass index (BMI) 35 ± 2 kg/m2] and seven lean (BMI 21 ± 1 kg/m2) adolescents aged 13–15 yr and compared them with nine lean adults (aged 21–27 yr, BMI 23 ± 1 kg/m2) during a two-step euglycemic-hyperinsulinemic clamp in combination with 1) a constant [2H5]glycerol (1.2 mg ⋅ m−2 ⋅ min−1) infusion to quantify glycerol turnover and 2) indirect calorimetry to estimate glucose and net lipid oxidation rates. In absolute terms, basal glycerol turnover was increased and suppression by insulin was impaired in obese adolescents compared with both groups of lean subjects ( P < 0.01). However, when the rates of glycerol turnover were adjusted for differences in body fat mass, the rates were similar in all three groups. Basal plasma free fatty acid (FFA) concentrations were significantly elevated, and the suppression by physiological increments in plasma insulin was impaired in obese adolescents compared with lean adults ( P < 0.05). In parallel with the high circulating FFA levels, net lipid oxidation in the basal state and during the clamp was also elevated in the obese group compared with lean adults. Net lipid oxidation was inversely correlated with glucose oxidation ( r = −0.50, P < 0.01). In conclusion, these data suggest that lipolysis is increased in obese adolescents (vs. lean adolescents and adults) as a consequence of an enlarged adipose mass rather than altered sensitivity of adipocytes to the suppressing action of insulin.

Inhibitors of phosphatidylinositol 3-kinase amplify insulin release from islets of lean but not obese mice

“…Based on islet volume and insulin secretory rates, it has been estimated that during maximal glucose stimulation insulin bathing the -cell approaches 100-200 nM (Zawalich et al 1975), a level at least 1000-fold greater than systemic concentrations of the hormone (Del Prato et al 1994, Robinson et al 1998. Even under nonstimulatory conditions, the level of insulin bathing the -cell must be far in excess of that bathing other insulinsensitive tissues such as liver, fat and muscle.…”

Adipocyte-specific reduction of phosphodiesterase 3B gene expression and its restoration by JTT-501 in the obese, diabetic KKAy mouse

“…The basal and catecholamine-stimulated rate of lipolysis as well as intracellular cAMP concentration and HSL activity is positively correlated with fat cell size (34±36). In fact, both the level of lipolysis and that of circulating FFA are increased in obese humans and animals (37,38). It is possible that the inactivation of PDE3B results in an increase in HSL activity, which, in turn, would lead to an enhanced rate of release of FFA.…”

Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning

“…Analysis of enrichments of 2 H-glucose and 2 H 5 -glycerol in plasma and infusates by gas chromatography and mass spectrometry was done as described elsewhere. 23,24 The glucose infusion rates were calculated during the last 30 min of the low and high insulin clamp and expressed as moles glucose per kg of lean body mass per min. Endogenous hepatic glucose production and glycerol turnover at baseline and during the two steps of the insulin clamp, along with the clamped glucose disposal rates, were calculated as previously reported.…”

“…Endogenous hepatic glucose production and glycerol turnover at baseline and during the two steps of the insulin clamp, along with the clamped glucose disposal rates, were calculated as previously reported. 23,24 In the basal state, we calculated an index of hepatic insulin resistance as the product of endogenous glucose production and the fasting insulin concentrations. 25 The rate of glucose metabolism and the insulin sensitivity during the hyperglycaemic clamp procedure were calculated as previously reported.…”