Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats

Abstract

The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R'g) was estimated using 2-[3H]-deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incorporation into glycogen in four different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R'g was 80, 150, 280, and 320 mU/1 for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R'g in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R'g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R'g and blood flow in different muscles. We conclude that there is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidative to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.

Acute blockade by endothelin-1 of haemodynamic insulin action in rats

“…Free and phosphorylated 2DG were separated by ion exchange chromatography and the radioactivity in each determined. Muscle 2DG uptake (R′g), which reflects glucose uptake into the muscle, was calculated using the counts from the individual muscles and the time-rate of change of arterial plasma radioactivity, as previously described by others [24,25].…”

Are cultured human myotubes far from home?

“…Insulin-stimulated glucose uptake is generally greater in slow twitch-enriched muscles than fast-twitch muscles (Zierath and Hawley, 2004). For example, white gastrocnemius in rat containing mostly type 2 fibers shows a 7-fold response to insulin, whereas glucose uptake increased 11-fold in red gastrocnemius (James, et al, 1985). Therefore ways to change the phenotype to a more oxidative one would improve the insulin sensitivity.…”

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

“…Individual frozen muscles were ground under liquid nitrogen and 100 mg muscle tissue was homogenised with 1.5 ml water using an Ultra Turrax (IKA, Wilmington, NC, USA). Free and phosphorylated 2D[ 3 H]G were separated by ion exchange chromatography using an anion exchange resin (AG1-X8) [14,15]. Biodegradable Counting Scintillant-BCA (Amersham Life Science) was added to each radioactive sample and radioactivity determined using a scintillation counter (LS3801, Beckman Instruments, Fullerton, CA, USA).…”

“…Biodegradable Counting Scintillant-BCA (Amersham Life Science) was added to each radioactive sample and radioactivity determined using a scintillation counter (LS3801, Beckman Instruments, Fullerton, CA, USA). From this measurement and a knowledge of plasma glucose and the time course of plasma radioactive 2DG disappearance, muscle 2DG uptake, which reflects glucose uptake into the muscle, was calculated as previously described by others [14,15].…”