Age-dependent development of insulin resistance of soleus muscle in genetically obese (ob/ob) mice

Abstract

The relationship between insulin binding and its biological effects was studied in soleus muscle of 3- to 15-wk-old genetically obese (ob/ob) mice. At 3 and 4 wk of age, soleus muscle from lean and obese mice bound similar amounts of insulin under equilibrium binding conditions. However, by 6 wk of age, insulin binding and total receptor concentration (Ro) were significantly decreased in soleus muscle from obese compared to lean mice. In addition lean and obese mice demonstrated an age-dependent decrease in insulin binding, Ro, and receptor affinity. At 4 wk of age, insulin-stimulated 2-deoxyglucose transport and glucose utilization were significantly lower in soleus muscle from obese mice and preceded alterations in insulin binding. The postmembrane decrease in insulin sensitivity was dissimilar for various pathways of glucose metabolism. Glucose conversion of glycogen, but not the glycolytic rate or glucose oxidation, remained sensitive to insulin stimulation. These data indicate that glucose transport and utilization rather than insulin binding may play the primary role in the development of insulin resistance of muscle in the obese diabetic syndrome.

Dysregulation of glucose transport and transporters in perfused hearts of genetically obese (fa/fa) rats

“…1). These findings corroborate those of others made in other muscle types [4][5][6] and suggest that, although the heart is not representative of the muscle mass, it may undergo -upon the occurrence of insulin resistance -changes that are analogous to those seen in other muscles. This strengthens the observations made during the present study, with regard to the state of the glucose transporters as assessed by the cytochalasin B-binding assay.…”

“…With regard to glucose uptake, it has been shown that basal, as well as insulin-stimulated glucose uptake, was decreased in most obesity syndromes studied [2,[4][5][6]. As is now well established in adipocytes [8,9] and also described in muscle [10], glucose transporting molecules (glucose transporters) are present both in the plasma and in some intracellular (microsomal) membranes.…”

“…It has been demonstrated to be present in vitro as well as in vivo (reviewed in 1), and bears on insulin receptor number [2]; insulin receptor autophosphylation [3]; glucose uptake [4,5]; glycolysis [4][5][6] and glycogen synthesis [7].…”

Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice

“…Glucose tolerance and insulin sensitivity deteriorate with age in mice (Grundleger et al, 1980;Bailey and Flatt, 1982;Carvalho et al, 1996). Therefore, metabolic experiments should be carried out on agematched mice.…”

Mecanismos associados ao desenvolvimento das complicações do diabetes tipo 2 em camundongos fêmeas ob/ob: papel preventivo do treinamento físico dinâmico aeróbio, resistido ou combinado

“…Adicionalmente, a resistência à insulina, por exemplo, é observada após a 3º-4º semana de vida (GRUNDLEGER et al, 1980). De fato, em nosso estudo, observamos que os animais com 12 semanas de vida apresentam maior intolerância à glicose, quando comparados aos animas com 4 semanas de vida.…”