Summary
We have measured specific binding of insulin-like growth factor I and growth hormone to renal plasma membranes from control, streptozotocin-diabetic, insulin-treated diabetic, uninephrectomised and combined diabetic-uninephrectomised male Wistar rats. Control, insulin-treated and uninephrectomised rats had similar body weights after 7 days (243±2 g), whereas diabetic and diabetic-uninephrectomised animals were significantly lighter (219±4 and 203±4 g, p<0.05). Blood glucose concentrations were similar in the diabetic and diabetic-uninephrectomised animals (around 26 mmol/l) but significantly lower in the insulin-treated group. Right kidney weight increased by 14% in the control, insulin-treated and sham-nephrectomised animals, by 33% in the diabetic group, 38% in the nephrectomised animals and 60% in the diabetic-nephrectomised group. The renal content of insulin-like growth factor I was similar and stable in the control, insulin-treated and sham-nephrectomised animals (208±14 ng/g wet weight) but rose to a peak of 669±35 ng/g in the diabetic group (p<0.001), 871±34 ng/g in the nephrectomised animals (p<0.001) and 1012±43 ng/g in the diabetic-uninephrectomised group (p<0.001). Maximum binding of insulin-like growth factor I fell on day 1 in the diabetic group (8.3±1.4 vs 5.2±0.71× 10− mol/l; p<0.01) but thereafter was identical to control animals. In the insulin-treated animals, maximum binding rose to 11.0±1.1×10−11 mol/l, significantly different from control and diabetic animals (p<0.01). Growth hormone binding fell acutely in both the diabetic and diabetic-nephrectomised animals (3.13±0.58 and 2.83±0.21 vs 7.77±0.68×10−12 mol/l; p<0.001 for both). Following uninephrectomy, maximum binding of insulin-like growth factor I and growth hormone was unchanged from control values. We conclude that the rise in renal content of insulin-like growth factor I which precedes the compensatory growth seen after induction of diabetes and uninephrectomy is not due to alterations in insulin-like growth factor I receptor binding and is independent of growth hormone binding.
Article PDF
Similar content being viewed by others
References
Seyer-Hansen K (1976) Renal hypertrophy in streptozotocin-diabetic rats. Clin Sci 51: 551–554
Flyvbjerg A, Thorlacius-Ussing O, Næraa R, Ingerslev J, Ørskov H (1988) Kidney tissue somatomedin C and initial renal growth in diabetic and uninephrectomised rats. Diabetologia 31: 310–314
Flyvbjerg A, Frystyk J, Thorlacius-Ussing O, Ørskov H (1989) Somatostatin analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomised rats. Diabetologia 32: 261–265
Stiles AD, Sosenko IRS, D'Ercole AJ, Smith BT (1985) Relation of kidney tissue somatomedin-C/Insulin-like growth factor I to postnephrectomy renal growth in the rat. Endocrinology 117: 2397–2401
Seyer-Hansen K (1977) Renal hypertrophy in experimental diabetes: relation to severity of diabetes. Diabetologia 13: 141–143
Flyvbjerg A, Ørskov H (1990) Kidney tissue insulin-like growth factor I and initial renal growth in diabetic rats: relation to severity of diabetes. Acta Endocrinol (Copenh) 122: 374–378
Seyer-Hansen K (1978) Renal hypertrophy in experimental diabetes: A comparison to compensatory hypertrophy. Diabetologia 14: 325–328
Flyvbjerg A, Frystyk J, Marshall SM (1990) Additive increase in kidney insulin-like growth factor I and initial renal enlargement in uninephrectomised-diabetic rats. Horm Metabol Res 22: 516–520
Daughaday WH, Hall K, Raben MS, Salmon WD Jn, Van den Brande JL, Van Wyk JJ (1972) Somatomedin: proposed designation for sulfation factor. Nature (London) 235: 107
D'Ercole AJ, Stiles AD, Underwood LE (1984) Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci 81: 935–939
Murphy LJ, Bell GI, Friesen HG (1987) Tissue distribution of insulin-like growth factor I and II messenger ribonucleic acid in the adult rat. Endocrinology 120: 1279–1282
Roberts CT Jr, Lasky SR, Lowe WL Jn, Seaman WT, LeRoith D (1987) Molecular cloning of rat insulin-like growth factor I complementary deoxyribonucleic acids: differential messenger ribonucleic acid processing and regulation by growth hormone in extrahepatic tissues. Mol Endocrinol 1: 243–248
Flyvbjerg A, Bornfeldt K, Marshall SM, Arnqvist H, Ørskov H (1990) Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. Diabetologia 33: 334–338
Fagin JA, Melmed S (1987) Relative increase in insulin-like growth factor I messenger ribonucleic acid levels in compensatory renal hypertrophy. Endocrinology 120: 718–724
Lajara R, Rotwein R, Bortz JD et al. (1989) Dual regulation of insulin-like growth factor I expression during renal hypertrophy. Am J Physiol 257: F252-F261
Polychronakos C, Guyda JH, Posner BI (1985) Increase in the type 2 insulin-like growth factor receptors in the rat kidney during compensatory growth. Biochem Biophys Res Commun 132: 418–423
Bhaumick B, Bala RM (1987) Binding and degradation of insulin-like growth factors I and II by rat kidney membrane. Endocrinology 120: 1439–1448
Abrass CK, Raugi GJ, Gabourel LS, Lovett DH (1988) Insulin and insulin-like growth factor I binding to cultured rat glomerular mesangial cells. Endocrinology 123: 2432–2439
Arnqvist HJ, Ballermann BJ, King GL (1988) Receptor for and effects of insulin and IGF-I in rat glomerular mesangial cells. Am J Physiol 254: C411–416
Conti FG, Striker LJ, Lesniak MA, MacKay K, Roth J, Striker GE (1988) Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells. Endocrinology 122: 2788–2795
Pillion DJ, Haskell JF, Meezan E (1988) Distinct receptors for insulin-like growth factor I in rat renal glomeruli and tubules. Am J Physiol 255: E504–512
Aron DC, Rosenzweig JL, Abboud HE (1989) Synthesis and binding of insulin-like growth factor I by human glomerular mesangial cells. J Clin Endocrinol Metab 68: 585–591
Hammerman MR, Rogers S (1987) Distribution of IGF receptors in the plasma membrane of proximal tubular cells. Am J Physiol 253: F841-F847
Marshall RN, Underwood LE, Voina SJ, Foushee DB, Van Wyk JJ (1974) Characterization of the insulin and somatomedin-C receptors in human placental cell membranes. J Clin Endocrinol Metab 39: 283–292
Lowry OH, Osebrough NJ, Fara AC, Randall RJ (1951) Protein measurements with the folin phenol reagents. J Biol Chem 193: 165–175
McPherson GA (1983) A practical computer-based approach to the analysis of radioligand binding experiments. Comput Programs Biomed 17: 107–114
Thorlacius-Ussing O, Flyvbjerg A, Jorgensen KD, Ørskov H (1988) Growth hormone restores normal growth in selenium treated rats without increase in circulating SMC. Acta Endocrinol (Copenh) 117: 65–72
Statistical package for the Social Sciences, SPSS Inc, Chicago, USA 1986
Werner H, Shen-Orr Z, Stannard B, Burguera B, Roberts CT, LeRoith D (1990) Experimental diabetes increases insulin-like growth factor I and II receptor concentration and gene expression in the kidney. Diabetes 39: 1490–1497
Suikkari A-M, Koivisto VA, Rutanen E-M, Yki-Jarvinen H, Karonen S-C, Seppala M (1988) Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding proteins. J Clin Endocrinol Metab 66: 266–272
Hirschberg R, Kopple JD (1989) Effects of growth hormone and IGF-I on renal function. Kidney Int 36 [Suppl 27]: S20-S26
Bornfeldt KE, Arnqvist HJ, Enberg B, Mathews LS, Norstedt G (1989) Regulation of insulin-like growth factor-I and growth hormone receptor gene expression by diabetes and nutritional state in rat tissues. J Endocrinol 122: 651–656
Tannenbaum GS (1981) Growth hormone secretory dynamics in streptozotocin diabetes: evidence of a role for endogenous circulating somatostatin. Endocrinology 108: 76–82
Andersson GL, Skottner A, Jennische E (1988) Immunocytochemical and biochemical localization of insulin-like growth factor I in the kidney of rats before and after uninephrectomy. Acta Endocrinol (Copenh) 119: 555–560
Hansson HA, Nilsson A, Isgaard J et al. (1988) Immunohistochemical localisation of insulin-like growth factor I in the adult rat. Histochemistry 89: 403–410
Bortz JD, Rotwein P, DeVol D, Bechtel PJ, Hansen VA, Hammerman R (1988) Focal expression of insulin-like growth factor I in the rat kidney collecting duct. J Cell Biol 107: 811–817
Mauer SM, Steffes MW, Ellis EN, Sutherland DER, Brown DM, Goetz FC (1984) Structural-functional relationships in diabetic nephropathy. J Clin Invest 74: 1143–1155
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marshall, S.M., Flyvbjerg, A., Frystyk, J. et al. Renal insulin-like growth factor I and growth hormone receptor binding in experimental diabetes and after unilateral nephrectomy in the rat. Diabetologia 34, 632–639 (1991). https://doi.org/10.1007/BF00400992
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00400992