Tissue-related changes in insulin receptor number and autophosphorylation induced by starvation and diabetes in rats.
Insulin action is subject to regulation at the level of the insulin receptor and at postreceptor levels. Starvation and diabetes are often associated with insulin resistance for glucose metabolism in various tissues. In muscle, fat, and liver, we examined whether changes in the functionality of the insulin receptor correlated with changes in insulin action in the starved and diabetic state. Insulin-stimulated receptor autophosphorylation reflects an early physiologic step in transmission of the insulin signal, and for that reason, changes in autophosphorylation activity of the insulin receptor were used as a marker to determine the functionality of the insulin receptor. Glycoprotein fractions prepared from skeletal muscle, diaphragm, epididymal fat, and liver of control, 3-day starved, short-term 3-day (S) diabetic (streptozotocin, 70 mg/kg intravenously), and long-term 6-month (L) diabetic (neonatal streptozotocin 100 micrograms/g intraperitoneally) rats were used in this study. Receptor activity was monitored by measuring insulin-stimulated [gamma-32P]adenosine triphosphate (ATP) receptor autophosphorylation. In addition, to obtain information about whether changes in receptor autophosphorylation are related to changes in receptor number, relative numbers of high-affinity insulin receptors were determined by affinity cross-linking of [125I]insulin to the receptor alpha-chain and quantitation of the yield of labeled receptor alpha-chain. Control, starved, S diabetic, and L diabetic rats had plasma insulin and glucose levels of 294 +/- 42, 90 +/- 24, 48 +/- 12, and 216 +/- 30 pmol/L and 6.7 +/- 0.2, 4.1 +/- 0.2, 23.3 +/- 0.7, and 21.6 +/- 2.9 mmol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Koopmans
S J
SJ
Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands.
Maassen
J A
JA
Sips
H C
HC
Radder
J K
JK
Krans
H M
HM
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003432:Cross-Linking Reagents; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism*; D013217:Starvation / Q000378:metabolism*
D003432:Cross-Linking Reagents; D007328:Insulin; D011972:Receptor, Insulin