Glucose clamp

A brief overview about the fundamental principles of the pathogenesis of skeletal muscle insulin resistance and its contribution to the development of type 2 diabetes mellitus is given in the following. Priority is given to the role of lipid metabolism, which is the main field of the reported spectroscopic studies. Furthermore, the technique of euglycemic hyperinsulinemic glucose clamp is described allowing determination of the individual insulin sensitivity of musculature. The role of IMCL in insulin resistance of the skeletal muscle is discussed. 

Before and after the dietary interventions, IMCL was measured in TA and SOL, and insulin sensitivity was assessed by a euglycemic hyperinsulinemic glucose clamp. 

Heinemann L, Ampudia-Blasco FJ. Glucose clamps with the Biostator a critical reappraisal. Hormone Metabolism Research 1994, 26, 579-583. 

Defronzo RA, Tobin JD, Andres R. Glucose clamp technique method for quantifying insulin-secretion and resistance. American Journal of Physiology 1979,237, E2I4 E223. 

DeFronzo, R.A., J.D. Tobin, and R. Andres. 1979. Glucose clamp technique a method for quantifying insulin... 

This is the fundamental relation for the glucose clamp. The value of GIR depends then on the changes in Jupt and HGO after insulin stimulation and the clamped value of the glucose concentration. Introducing the uptake from Eq. (29) gives ... 

Fig. 6.20 Relation between the fluxes and insulin concentration during a glucose clamp. The glucose infusion rate, GIR, is calculated according to Eq. (46).

Metabolic blood parameters are assayed in anesthetized male rats using a modified method of glucose clamp studies in rodents (Terrettaz and Jeanrenaud 1983). Four to 6 rats per group (vehicle control and one dose of the candidate compound) are used. Rats are anesthetized with an intraperitoneal injection of pentobarbital sodium (60 mg/kg), tracheotomized, and one jugular vein per rat is cannulated for intravenous infusion the other vein is prepared for collection of blood samples. Anesthesia is maintained for up to 7 hours by subcutaneous infusion of pentobarbital sodium (adjusted to the anesthetic depth of the individual animal about 24 mg/kg/h). Body temperature is monitored with a rectal probe thermometer, and temperature is maintained at 37 °C by means of a heated surgical table. Blood samples for glucose analysis (10 il) are obtained from the tip of the tail every 15 minutes, and for lactate analysis (20 p.1) every... 

Euglycemic Hyperinsulinemic Glucose Clamp Technique in Anesthetized Rats... 

Schoelch C, Kuhlmann J, Gossel M et al. (2004) Characterization of adenosine-Aj-receptor-mediated antilipolysis in rats by tissue-microdialysis, 1 H-spectroscopy and glucose clamp studies. Diabetes 53 1920-1926 Smith D, Rossetti L, Ferrannini E et al. (1987) In vivo glucose metabolism in the awake rat Tracer and insulin clamp studies. Metabolism 36 1167-1174 Terrettaz J, Jeanrenaud B (1983) In vivo hepatic and peripheral insulin resistance in genetically obese (fa/fa) rats. Endocrinology 112 1346-1351... 

For the assessment of the side effect potential of the candidate compound on peripheral insulin sensitivity, multiple oGTTs can be performed during the treatment period or the animal study is finished by a hyperinsulinemic-euglycemic glucose clamp study. 

Tominaga et al. (1993) used the glucose clamp-technique in streptozotocin-induced diabetic rats. 

Lee and Olefsky (1995) studied the effects of troglitazone in normal rats with the euglycemic glucose clamp technique. 

CRITICAL ASSESSEMENT OF THE METHOD The results of metabolic tissue parameters in liver, and muscle must be interpreted carefully, when a hyperinsulinemic-euglycemic glucose clamp study is performed at the end of the treatment period. Under clamp conditions these tissue parameters are mainly influenced by the hyperinsulinemic condition during the clamp study than by the compound s effect itself. 

Rave K, Flesch S, Kuhn-Velten WN, Hompesch BC, Heinemann L, Heise T. Enhancement of blood glucose lowering effect of a sulfonylurea when coadministered with an ACE inhibitor results of a glucose-clamp study. Diabetes Metab Res Rev (2005) 21, 459-64. 

Besides salt sensitivity, insulin resistance is also commonly observed in CKD. We tested whether MGO could increase insulin resistance in rats using glucose clamp technique. Increase in insulin resistance was observed in rats treated with MGO, which was completely reduced by administration of N-acetyl cysteine and carbonyl scavengers. ... 

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