The Glucose Clamp

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 ... 

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

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. 

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... 

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. 

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. 

To cause adsorption of the glucose-1-phosphate by the IR-45, gently pour the acidic solution treated with Dowex 50 (steps 13 and 14 of the protocol for Day 2) onto the column, avoiding the introduction of air bubbles into the resin bed. Open the screw clamp and adjust the flow rate to about 15 ml/min. Pass the entire solution through the IR-45 resin without permitting air to enter the column. 

In NIDDM patients, benfluorex treatment improves glucose tolerance and lowers blood glucose under conditions which do not affect body weight [388-390], By the euglycaemic clamp technique, improvements both in peripheral glucose utilization [390-392] and hepatic glucose output [391] have been demonstrated. Thus overall benfluorex increases insulin sensitivity. 

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