The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization

Abstract

The effect of insulin on the disposal of intravenous glucose was examined employing the euglycemic insulin clamp technique in 24 normal subjects. When the plasma insulin concentration was raised by approximately 100 μU/ml, total glucose metabolism rose to 6.63 ± 0.38 mg/kg · min. Basal splanchnic (hepatic venous catheter technique) glucose production, 2.00 increased only slightly. These results suggest that the ability of higher doses of insulin to further stimulate glucose metabolism is primarily the result of increased glucose storage by peripheral tissues, most likely muscle. 0.15 ± mg/kg · min, reverted to a small net glucose uptake which averaged 0.33 mg/kg · min over the ensuing 2 h. This represented only 5% of the total glucose metabolized. In contrast, leg (femoral venous catheterization) glucose uptake rose from 1.18 ± 0.14 to 8.40 ± 1.06 mg/kg of leg wt. per min. If all muscles in the body respond similarly to those in the leg, muscle would account for 85% of the total glucose metabolism. To determine the relative contributions of glucose oxidation versus glucose storage by peripheral tissues following hyperinsulinemia, we performed euglycemic insulin clamp studies in combination with indirect calorimetry. Basal glucose oxidation, 1.21 ± 0.10 mg/kg min, rose to 2.28 ± 0.16 (P < 0.01), and this increase above baseline accounted for only 20% of the total glucose metabolized, 5.44 ± 0.38 mg/kg · min. Following insulin, glucose storage increased to 3.18 ± 0.34 mg/kg min and was responsible for 59% of the total glucose metabolized. These results indicate that the primary effect of insulin on muscle tissue is to enhance glucose storage, presumably as glycogen. When a higher degree of hyperinsulinemia (163 ± 19 μl/ml) was created while maintaining euglycemia, total glucose metabolism (7.99 ± 0.58) and glucose storage (5.30 ± 0.80) both increased (P < 0.01) compared with the lower dose insulin clamp study, but glucose oxidation (2.70 ± 0.16 mgμkg min)increased only slightly. These results suggest that the ability of higher doses of insulin to further stimulate glucose metabolism is primarily the result of increased glucose storage by peripheral tissues, most likely muscle.

Sedimentation and immunological analyses of GLUT4 and α2‐Na,K‐ATPase subunit‐containing vesicles from rat skeletal muscle: evidence for segregation

“…Among the best-documented responses in skeletal muscle to insulin are the activation of glucose transport and the Na,KATPase [1][2][3][4]. Skeletal muscle expresses both the GLUT1 and GLUT4 glucose transporters but it is the mobilization of GLUT4, from an intracellular store to the plasma membrane (PM), that explains the observed increase in glucose transport in response to insulin binding [5][6][7][8].…”

High-fat diet, muscular lipotoxicity and insulin resistance

“…a reduced glucose disposal and impaired inhibition of hepatic glucose output at a given concentration of insulin (McGarry, 2002). A major contribution to whole-body insulin resistance comes from the skeletal muscle, as revealed by classical work by DeFronzo et al (1981), who have shown a 45% reduction in leg glucose uptake following a hyperinsulinaemic euglycaemic clamp in patients with type 2 diabetes and a strong positive correlation (r 0 . 70, P <0 .…”

Effect of 2-month detraining on body composition and insulin sensitivity in young female dancers

“…Another possibility that accounts for the reduced insulin sensitivity among those detrained female young dancers was the reduction in skeletal muscle GLUT4 protein expression. Skeletal muscle is the main tissue for postprandial glucose disposal, 19 while GLUT4 protein is the main isoform of glucose transporter expressed in skeletal muscle. This protein has been found to be elevated by exercise 20 and downregulated following short-term detraining.…”