Summary
It has recently been demonstrated that immunoassayable kidney insulin-like growth factor I concentration increases 24–48 h after induction of diabetes, preceding the initial renal hypertrophy. To elucidate whether this increase is due to increased local production we studied rat kidney insulin-like growth factor I gene expression during the first four days after induction of streptozotocin diabetes. Eighteen hours after injection with streptozotocin the diabetic animals were divided into two groups, one of which was treated with insulin, and daily for four days animals from each group were taken out for investigation. After four days the wet kidney weight had increased from baseline by 20% (from 687±23 to 827±6mg (mean±SEM), p < 0.01) in the untreated diabetic group, while no significant increase occurred in the insulin-treated group (687±23 vs 732±21 mg, NS). Kidney insulin-like growth factor I increased rapidly from baseline, the rise amounting to 52% after 48 h (from 271±11 to 411±32 ng/g, p < 0.01) with a decline to control level on day four in the untreated diabetic group. Kidney insulin-like growth factor I remained unchanged in the insulin-treated diabetic group. Insulin-like growth factor I mRNA was measured by solution-hybridization assay. No differences were found in kidney insulin-like growth factor I mRNA between the two diabetic groups over the study period, while in liver, insulin-like growth factor I mRNA tended to be lower on day four in diabetic rats when compared to insulin-treated rats (p=0.07). These results show that the increase in kidney insulin-like growth factor I during initial renal hypertrophy in experimental diabetes is not associated with an elevated level of kidney insulin-like growth factor I mRNA and suggest that other, possibly translational, mechanisms are responsible for insulin-like growth factor accumulation in the kidney.
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References
Mogensen CE, Andersen MJF (1973) Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 22: 706–712
Seyer-Hansen K (1976) Renal hypertrophy in streptozotoci-ndiabetic rats. Clin Sci 51: 551–555
Flyvbjerg A, Thorlacius-Ussing O, Næraa R, Ingerslev J, Ørskov H (1988) Kidney tissue somatomedin C and initial renal growth in diabetic and uninephrectomized rats. Diabetologia 31: 310–314
Mogensen CE (1986) Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scand J Clin Lab Invest 46: 201–206
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 uninephrectomized rats. Diabetologia 32: 261–265
Daughaday WH, Hall K, Raben MS, Salmon WD Jr, Van den Brande JL, Van Wyk JJ (1972) Somatomedin: proposed designation for sulphation factor. Nature 235: 107
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
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
Murphy LJ, Bell GI, Frisen HG (1987) Tissue distribution of insulin-like growth factor I and II ribonucleic acid in the adult rat. Endocrinology 120: 1279–1282
Stiles AD, Sosenko IRS, D'Ercole AJ, Smith BT (1985) Relations of kidney tissue somatomedin-C/insulin-like growth factor I to postnephrectomy renal growth in the rat. Endocrinology 117: 2397–2401
Andersen 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
Lajara R, Rotwein P, Bortz JD, Hansen VA, Sadow JL, Betts CR, Rogers SA, Hammerman MR (1989) Dual regulation of insulin-like growth factor I expression during renal hypertrophy. Am J Physiol 257: F252-F261
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
Shimatsu A, Rotwein P (1987) Mosaic evolution of the insulin-like growth factors. Organization, sequence, and expression of the rat 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 promotor. Nucl Acids Res 12: 7035–7056
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
Fagin JA, Roberts CT, LeRoith D, Brown AT (1989) Coordinate decrease of tissue insulin-like growth factor I posttranscriptional alternative mRNA transcripts in diabetes mellitus. Diabetes 38: 428–434
Clemmons DR, Underwood LE, Van Wyk JJ (1981) Hormonal control of immunoreactive somatomedin production by cultured human fibroblasts. J Clin Invest 67: 10–19
Conti FG, Striker LJ, Elliot SJ, Andreani D, Striker GE (1988) Synthesis and release of insulin like growth factor I by mesangial cells in culture. Am J Physiol 255: F1214-F1219
Seyer-Hansen K (1977) Renal hypertrophy in experimental diabetes: Relation to severity of diabetes. Diabetologia 13: 141–143
Hostetter TH, Troy JL, Brenner BM (1981) Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int 19: 410–415
Seyer-Hansen K (1983) Renal hypertrophy in experimental diabetes mellitus. Kidney Int 23: 643–646
Goldstein S, Sertich GJ, Levan KR, Phillips LS (1988) Nutrition and somatomedin. XIX. Molecular regulation of insulin-like growth factor-1 in streptozotocin-diabetic rats. Molec Endocrinol 2: 1093–1100
Froesch ER, Schmid S, Schwander J, Zapf J (1985) Actions of insulin-like growth factors. Ann Rev Physiol 47: 443–467
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
Rotwein P, Burgess SK, Milbrandt JD, Krause JE (1988) Differential expression of insulin-like growth factor genes in rat central nervous system. Proc Natl Acad Sci USA 85: 265–269
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Flyvbjerg, A., Bornfeldt, K.E., Marshall, S.M. et al. Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. Diabetologia 33, 334–338 (1990). https://doi.org/10.1007/BF00404636
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DOI: https://doi.org/10.1007/BF00404636