Insulin-stimulated Glucose Uptake In Skeletal Muscle Research Articles

Possible synergistic effect of ACE inhibition and calcium-channel blockade on insulin sensitivity in insulin-resistant type II diabetic hypertensive patients.

So-called insulin resistance is a frequent phenomenon and a marker of increased risk for both type II diabetes mellitus and atherosclerosis. Today, insulin resistance is widely understood as a tissue- and pathway-specific defect of insulin-stimulated glucose uptake into skeletal muscle that is compensated for by hyperinsulinemia, leading to a cluster of undesirable hypertensiogenic, diabetogenic, and atherogenic processes. Additional defects of insulin-stimulated muscle blood flow and cellular kation balance are presently attracting increasing awareness. Clinical and experimental evidence suggests that angiotensin-converting enzyme (ACE) inhibition ameliorates both insulin-stimulated skeletal-muscle glucose uptake and blood flow in insulin-resistant states by a direct stimulation of cellular glucose uptake, which appears to be kinin-mediated. This improvement of insulin sensitivity could mean not only improvement of glucose metabolism, but also reduction of chronically elevated serum insulin and the ensuing atherogenic consequences (hyper- and dyslipidemia, sympathetic overactivity, growth of vascular smooth-muscle cells, hypertension, etc.). Ca(2+)-channel blockers that do not increase heart rate appear to exert direct antiatherogenic effects while being metabolically neutral. Thus, the combination of Ca(2+)-channel blockade by sustained release verapamil and ACE inhibition by trandolapril in insulin-resistant type II diabetic patients with essential hypertension appears to be promising in terms of possible synergistic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of age and high sucrose diet on 2-deoxyglucose uptake in perfused hindlimb.

The purpose of this investigation was to evaluate insulin-stimulated skeletal muscle glucose uptake in male Fischer 344 rats, age 6, 12, and 27 mo, fed either a sucrose (S: 66.6% sucrose, 17.6% protein, 6.4% fat) or sucrose-free (SF: 66.6% starch, 17.6% protein, 6.4% fat) diet for 3 mo. Skeletal muscle glucose uptake (Rg) in perfused hindlimbs was estimated from the uptake and subsequent phosphorylation of radiolabeled 2-deoxyglucose (2DG) in the gastrocnemius (GN), extensor digitorum longus (EDL), and soleus (SOL) muscles. Rat hindlimbs were perfused at a rate of 10 ml.min-1 with a modified Krebs Henseleit buffer containing bovine red blood cells (hematocrit: 40%) and 5.85 mmole.L-1 glucose along with 358 pmoles.L-1 followed by 3580 pmoles.L-1 insulin. There was no effect of diet on plasma glucose levels measured at weeks 1, 7, and 11 of the dietary period. A significant effect of age on estimated glucose uptake in the GN was demonstrated due primarily to greater uptake in the 27-mo compared to the 6-mo-old animals. This significant effect of age was not evident in the EDL or SOL, nor were there significant effects of diet in any muscle. These data suggest that insulin-stimulated glucose uptake in perfused hindlimbs is not attenuated with senescence or with the feeding of a sucrose diet for 3 months.

Physiological Levels of Plasma Non-Esterified Fatty Acids Impair Forearm Glucose Uptake in Normal Man

1. The purpose of the present study was to maintain physiological plasma non-esterified fatty acid levels and to (i) examine their effect on skeletal muscle insulin-stimulated glucose uptake and metabolite exchange using the forearm technique, and (ii) evaluate their effect on whole-body glucose uptake and fuel oxidation. 2. Intralipid (10%) and heparin (Lipid) or saline (Control) was administered to eight healthy male subjects on separate occasions for 210 min. Insulin, glucagon and somatostatin were administered from 60 to 210 min in each study and euglycaemia was maintained. 3. Plasma non-esterified fatty acid levels plateaued at 420 +/- 50 mumol/l with the Lipid infusion but were completely suppressed during the Control clamp. Forearm non-esterified fatty acid uptake increased with the Lipid infusion (+50 +/- 10 nmol min-1 100 ml-1 of forearm) and was accompanied by a significant decrease in forearm glucose uptake (+3.23 +/- 0.25 versus +3.65 +/- 0.35 mumol min-1 100 ml-1 of forearm, Lipid and Control, respectively; P less than 0.05) and alanine release (-84 +/- 12 versus -113 +/- 15 nmol min-1 100 ml-1 of forearm, Lipid and Control, respectively; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Histochemical, biochemical, and contractile properties of red, white, and intermediate fibers.

Histochemical, biochemical, and contractile properties of red, white, and intermediate fibers.

INJURED BABY.

<h3>Abstract</h3> Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analyses of primary myocytes from lean insulin-sensitive (LN) and obese insulin-resistant (OB) individuals revealed several species of lysophospholipids (lyso-PL) that were differentially-abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle-specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lyso-PC/PC, concomitant with greater insulin sensitivity <i>in vivo</i> and insulin-stimulated skeletal muscle glucose uptake <i>ex vivo</i>. Absence of LPCAT3 reduced phospholipid packing of the cellular membranes and increased plasma membrane lipid clustering, suggesting that LPCAT3 affects insulin receptor phosphorylation by modulating plasma membrane lipid organization. In conclusion, obesity accelerates the skeletal muscle Lands cycle, whose consequence might induce the disruption of plasma membrane organization that suppresses muscle insulin action.