Cold exposure potentiates the effect of insulin on in vivo glucose uptake

Abstract

The effects of cold exposure (48 h at 4 degrees C) and insulin injection (0.5 U/kg iv) on the rates of net 2-[3H]deoxyglucose uptake (Ki) in peripheral tissues were investigated in warm-acclimated rats (25 degrees C). Cold exposure and insulin treatment independently increased Ki values in skeletal muscles (soleus, extensor digitorum longus, and vastus lateralis), heart, white adipose tissue (subcutaneous, gonadal, and retroperitoneal), and brown adipose tissue (P less than 0.01). The effects of cold exposure were particularly evident in brown adipose tissue where the Ki increased greater than 100 times. When the two treatments were combined (insulin injection in cold-exposed rats), it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an "insulin-like" effect on Ki that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake.

Thyroid Hormone Augments GLUT4 Expression and Insulin-Sensitive Glucose Transport System in Differentiating Rat Brown Adipocytes in Culture.

“…It seems, therefore, most likely that the increased GLUT4 contents account for the improved sensitivity of glucose transport to insulin. In accordance with this, it has been reported that the increased GLUT4 expression in BAT under cold environment is associated with potentiation of the insulin effect on glucose uptake in vivo [33].…”

Cold-induced PGC-1α expression modulates muscle glucose uptake through an insulin receptor/Akt-independent, AMPK-dependent pathway

“…Studies of insulin production and action and of glucose uptake in homeothermic animals exposed to cold revealed that, in this particular physiological condition, glucose is efficiently mobilized, despite low blood insulin levels and an apparent tissue-specific resistance to insulin's action (7,11,41,45). Therefore, it became clear that mechanisms that act independently of insulin signaling through the IR-IR substrates (IRSs)-Akt pathway play an important role in the control of glucose disposal in coldexposed animals.…”

“…The exposure of homeothermic animals to a cold environment has been widely used as a model for studying glucose homeostasis and insulin action (11,45). Under this condition, animals mobilize glucose more efficiently, despite molecular resistance to insulin signal transduction in skeletal muscle and adipose tissue (11).…”

The Role of Insulin in Norepinephrine Turnover and Thermogenesis in Brown Adipose Tissue after Acute Cold-Exposure.

“…The work of others has demonstrated a marked increase in the sensitivity to insulin induced by cold-exposure (Vallerand et al, 1986(Vallerand et al, , 1987Bartness et al, 1986aBartness et al, , 1986b. Cold-exposure potentiates the effect of insulin on in vivo glucose uptake in BAT at a normal insulin level, and glucose would principally be utilized in de novo lipogenesis as fuel for BAT thermogenesis.…”