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  • Insulin resistance  (1)
  • Key words GLUT 4, glucose transporter, insulin resistance, (fa/fa) rats, GLUT 1, Zucker rats, skeletal muscle, perineurial sheath, crude membranes, hyperglycaemia, metformin.  (1)
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  • 1
    ISSN: 1432-0428
    Keywords: Insulin resistance ; insulin receptor ; tyrosine kinase ; skeletal muscle ; Type 2 (non-insulin-dependent) diabetes mellitus ; insulin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently, we demonstrated insulin resistance due to reduced glucose storage in young relatives of Type 2 diabetic patients. To investigate whether this was associated with a defective insulin receptor kinase, we studied ten of these young (27±1 years old) non-obese glucose tolerant first degree relatives of patients with Type 2 diabetes and eight matched control subjects with no family history of diabetes. Insulin sensitivity was assessed by a hyperinsulinaemic, euglycaemic clamp. Insulin receptors were partially purified from muscle biopsies obtained in the basal and the insulin-stimulated state during the clamp. Insulin binding capacity was decreased by 28% in the relatives (p〈0.05) in the basal biopsy. Tyrosine kinase activity in the receptor preparation was decreased by 50% in both basal and insulin-stimulated biopsies from the relatives. After stimulation with insulin “in vitro”, kinase activity was reduced in the relatives in basal (p〈0.005) and insulin-stimulated (p〈0.01) biopsies and also when expressed per insulin binding capacity (p≈0.05). Insulin stimulation of non-oxidative glucose metabolism correlated with “in vitro” insulin-stimulated tyrosine kinase activity (r=0.61, p〈0.01) and also when expressed per binding capacity (r=0.53, p〈0.025). We suggest that the marked defect in tyrosine kinase activity in partially purified insulin receptors from skeletal muscle is an early event in the development of insulin resistance and contributes to the pathophysiology of Type 2 diabetes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words GLUT 4, glucose transporter, insulin resistance, (fa/fa) rats, GLUT 1, Zucker rats, skeletal muscle, perineurial sheath, crude membranes, hyperglycaemia, metformin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recently, we demonstrated that approximately 60 % of GLUT 1 in a crude membrane fraction of rat skeletal muscle originates from perineurial sheaths. To study the in vivo regulation of GLUT 1 expression in different tissues in muscles, we measured the level of GLUT 1 in crude muscle membranes and in perineurial sheaths in diabetic (fa/fa) Zucker rats and lean controls, with and without metformin treatment. The GLUT 1 concentration in perineurial sheaths was identical in all four groups of rats, both when measured by quantitative immunofluorescence and by immunoblotting and densitometry. In a fraction of crude membranes of soleus muscles GLUT 1 expression was more than two-fold higher in (fa/fa) rats than in lean controls (p〈0.005). Metformin treatment significantly elevated GLUT 1 in control rats (p〈0.05) and tended to decrease GLUT 1 in diabetic rats (p〈0.075). The expressions of GLUT 1 and GLUT 4 in crude muscle membranes were inversely correlated (p〈0.01), and GLUT 1 expression correlated positively with fasting glucose (p〈0.05). In conclusion, GLUT 1 expression in perineurial sheaths is unaffected by alterations in glucose homeostasis and by the genes responsible for obesity and diabetes in the Zucker rat. GLUT 1 expression in a crude membrane fraction of soleus muscle is increased in the diabetic animals, likely due to an increased expression in muscle cells proper. [Diabetologia (1994) 37: 443–448]
    Type of Medium: Electronic Resource
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