Summary
Initial diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I suggesting that insulin-like growth factor I may be implicated in diabetic kidney growth. The present study was undertaken to examine the effects of exogenous insulin-like growth factor I infusion on diabetic renal hypertrophy at a time when renal insulin-like growth factor I concentration had returned to normal and the initial steep kidney growth rate had diminished to a much slower rate. Groups of rats with diabetes duration of 5 days were infused s. c. for 4 subsequent days with equimolar concentrations of insulin-like growth factor I (36 nmol/day) or insulin (35 nmol/day). Insulin infusion lowered blood glucose to a normal level within 2 days and induced an average body-weight gain of 9.3±0.6 g/day. Insulin-like growth factor I infused diabetic rats maintained the original diabetic state with blood glucose levels comparable to those of 0.154 mol/l NaCl-infused diabetic rats, but had nevertheless an average body-weight gain of 6.8±1.0 g/day while untreated diabetic rats had a lower body-weight gain amounting to 3.3±0.8 g/day (p<0.01). The kidney weight at day 9 in untreated diabetic animals was about 25% greater than that of non-diabetic control animals, while in insulin-like growth factor I treated diabetic rats a further increase (p<0.05) was seen, amounting to 36 % above control level. No increase was seen in the insulin-treated diabetic group. Whole kidney protein, RNA and DNA estimations indicated that, in 0.154 mol/l NaCl-infused diabetic animals, the kidney growth after 9 days constituted a mixture of cellular hypertrophy and hyperplasia while the excess kidney weight increase obtained in insulin-like growth factor I infused diabetic rats was due mainly to hypertrophy. The kidney content of immunoreactive insulin-like growth factor I at day 9 in insulin-like growth factor I infused diabetic rats was on average 85% greater than in 0.154 mol/l NaCl-infused diabetic and non-diabetic control groups, while no differences were found in insulin-like growth factor I mRNA levels. In conclusion, insulin-like growth factor I administration initiated after 5 days of diabetes, with restoration of high kidney insulin-like growth factor I levels similar to those seen after 1–2 days of diabetes, accelerates renal growth, supporting the concept that the early kidney insulin-like growth factor I accumulation may be the stimulus for initial diabetic kidney hypertrophy.
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References
Seyer-Hansen K (1983) Renal hypertrophy in experimental diabetes. Kidney Int 23: 643–646
Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311: 89–93
Cortes P, Lewin NW, Dumler F, Rubenstein AH, Verghese CP, Venkatachalam KK (1980) Uridine triphosphate and RNA synthesis during diabetes-induced kidney growth. Am J Physiol 238: E349-E357
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
Flyvbjerg A, Bornfeldt KE, Arnqvist HJ, Ørskov H (1990) Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. Diabetologia 33: 334–338
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
Flyvbjerg A, Frystyk J, Marshall SM (1990) Additive increase in kidney insulin-like growth factor I and initial renal enlargement in uninephrectomized-diabetic rats. Horm Metab Res 22: 516–520
D'Ercole AJ, Stiles AD, Underwood LE (1984) Tissue concentration of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc Natl Acad Sci USA 81: 935–939
Durnam DM. Palmiter RD (1983) A practical approach for quantitating specific mRNAs by solution hybridization. Anal Biochem 131: 385–393
Labarca C, Paigen K (1980) A simple, rapid and sensitive DNA assay procedure. Anal Biochem 102: 344–352
Mathews LS, Norstedt G, Palmiter RD (1986) Regulation of insulin-like growth factor I gene expression by growth hormone. Proc Natl Acad Sci USA 83: 9343–9347
Shimatsu A, Rotwein P (1987) Mosaic evolution of the insulin-like growth factor I gene. J Biol Chem 262: 7894–7900
Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR (1984) Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucl Acids Res 12: 7035–7056
Munro HN, Fleck A (1966) The determination of nucleic acids. Methods Biochem Anal 14: 113–176
Burton K (1956) A study of the conditions and mechanism of the diphenylamine reaction for a calorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323
Lowry OH, Osebrough NJ, Fara AL, Randall RL (1951) Porcine measurements with the folin phenol reagens. J Biol Chem 193: 165–175
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
Arnqvist HJ, Ballerman BJ, King GL (1988) Receptors for and effects of insulin and IGF-I in rat glomerular mesangial cells. Am J Physiol 254: C411-C416
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-E512
Marshall SM, Flyvbjerg A, Frystyk J, Korsgaard L, Ørskov H (1991) Renal insulin-like growth factor I and growth hormone binding in experimental diabetes and after unilateral nephrectomy. Diabetologia 34: 632–639
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 kidney. Diabetes 39: 1490–1497
Ooi GT (1990) Insulin-like growth factor-binding proteins (IGFBPs): more than just 1, 2, 3. Mol Cell Endocrinol 71: C39-C43
Unterman TG, Oehler DT, Becker RE (1989) Identification of a Type 1 insulin-like growth factor binding protein (IGFBP) in serum from rats with diabetes mellitus. Biochem Biophys Res Commun 163: 882–887
Böni-Schnetzler M, Binz K, Mary JL, Schmid C, Schwander J, Froesch ER (1989) Regulation of hepatic expression of IGF-I and fetal IGF binding protein mRNA in streptozotocin-diabetic rats. FEBS Lett 251: 253–256
Zapf J, Hauri C, Waldvogel M et al. (1989) Recombinant human insulin-like growth factor I induces its own specific carrier protein in hypophysectomized and diabetic rats. Proc Natl Acad Sci USA 86: 3813–3817
Tannenbaum GS (1981) Growth hormone secretion dynamics in streptozocin diabetes: evidence of a role for endogenous somatostatin. Endocrinology 108: 76–82
Robinson ICAF, Clark RG, Carlsson LMS (1987) Insulin, IGF-I and growth in diabetic rats. Nature 326, 549
Scheiwiller E, Guler HP, Merryweather J et al. (1986) Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I. Nature 323: 169–171
Berelowitz M, Szabo M, Froman LA, Firestone S, Chu L, Hintz RL (1981) Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and the pituitary. Science 212: 1279–1281
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Flyvbjerg, A., Bornfeldt, K.E., Ørskov, H. et al. Effect of insulin-like growth factor I infusion on renal hypertrophy in experimental diabetes niellitus in rats. Diabetologia 34, 715–720 (1991). https://doi.org/10.1007/BF00401516
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DOI: https://doi.org/10.1007/BF00401516