glycogen and Obesity--Morbid

The partitioning of glucose toward glycolytic end products rather than glucose oxidation and glycogen storage is evident in skeletal muscle with severe obesity and type 2 diabetes. The purpose of the present study was to determine the possible mechanism by which severe obesity alters insulin-mediated glucose partitioning in human skeletal muscle.. Primary human skeletal muscle cells (HSkMC) were isolated from lean (BMI = 23.6 ± 2.6 kg/m. These data suggest that with severe obesity the partitioning of glucose toward anaerobic glycolysis in response to insulin is a resilient characteristic of human skeletal muscle. This altered glucose partitioning appeared to be due, at least in part, to a reduction in TCA cycle flux.

Topics: Adult; Carbohydrate Metabolism; Cells, Cultured; Citric Acid Cycle; Female; Glycogen; Glycolysis; Humans; Male; Muscle Fibers, Skeletal; Obesity, Morbid; Primary Cell Culture; Tricarboxylic Acids

Roux-en-Y gastric bypass (RYGB) surgery has been shown to induce positive metabolic adaptations for individuals with severe obesity (body mass index ≥40 kg/m. To investigate the acute and chronic effects of RYGB surgery on insulin-stimulated glucose metabolism in cultured human primary myotubes derived from nondiabetic severely obese humans.. East Carolina University Bariatric Surgery Center and East Carolina Diabetes and Obesity Institute.. Primary human skeletal muscle cells were isolated from biopsies obtained from 8 women with severe obesity before, 1 month, and 7 months following RYGB surgery. Glucose metabolism, glycogen content, and insulin signal transduction were determined in differentiated myotubes.. Insulin-stimulated glycogen synthesis and glucose oxidation increased in human myotubes derived from patients with severe obesity at both 1 and 7 months post-RYGB. However, there were no alterations indicative of enhanced insulin signal transduction. At 1 month post-RYGB, muscle glycogen levels were lower (-23%) and phosphorylation of acetyl CoA carboxylase 2 (ACC2) was elevated (+16%); both returned to presurgery levels at 7 months after RYGB in myotubes derived from patients. At 7 months post-RYGB, there was an increase in peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) protein content (+54%).. These data indicate that insulin action intrinsically improves in cultured human primary myotubes derived from nondiabetic severely obese patients following RYGB surgery; however, the cellular alterations involved appear to consist of distinct acute and chronic components.

Topics: Acute Disease; Adult; Biopsy; Cells, Cultured; Chronic Disease; Female; Follow-Up Studies; Gastric Bypass; Glucose; Glycogen; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Muscle Fibers, Skeletal; Obesity, Morbid; Postoperative Period; Signal Transduction; Time Factors; Weight Loss

Skeletal muscle contributes significantly to reduced insulin-stimulated glucose disposal in patients with obesity and non-insulin-dependent (type II) diabetes mellitus (NIDDM). The biochemical basis for insulin resistance is not known but may involve reduced glucose transport and/or a defect in intracellular pathways for glucose disposal. To address this question, we measured basal and insulin-stimulated glucose oxidation, glycogen formation, and nonoxidative glycolysis (lactate and amino acid release) in an incubated muscle preparation from nonobese and morbidly obese patients with and without NIDDM. Pathways of glucose disposal were also determined in muscle of obese NIDDM patients incubated under hyperglycemic (20 mmol/L) conditions, which increases glucose uptake by mass action. Under basal conditions (no insulin present) there were no significant differences in glycogen formation or glucose oxidation between nonobese control, obese nondiabetic, or obese diabetics. Lactate release was significantly higher in obese controls compared to nonobese controls in the basal state at 5 mmol/L glucose (10.2 +/- 2.8 v 24.7 +/- 3.5 nmol/min/g, P < .05). Under maximal insulin-stimulated conditions, rates of glycogen formation, glucose oxidation, and nonoxidized glycolysis increased 1.9-, 2.3-, and 2.2-fold over basal (P < .05) in nonobese controls. By contrast, insulin was ineffective at stimulating significant increases in any metabolic pathway of glucose disposal in muscle of obese or obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Analysis of Variance; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glucose; Glycogen; Glycolysis; Humans; In Vitro Techniques; Insulin; Male; Middle Aged; Muscles; Obesity; Obesity, Morbid; Oxidation-Reduction