Summary
We have investigated whether the previously demonstrated stimulatory actions of growth hormone on DNA synthesis and (pro)insulin biosynthesis and release of isolated adult rat islets of Langerhans are mediated by an autocrine release of somatomedin-C/insulin-like growth factor I (SM-C/IGF I). In medium containing 1% fetal calf serum, the presence of 16.7 mmol/l glucose, or 2.7 mmol/l glucose supplemented with a concentrate of essential amino acids, caused a significant increase in 3H-thymidine incorporation and insulin release compared to 2.7 mmol/l glucose alone but no increase in SM-C/IGFI release. Further supplementation with 1 μg/ml growth hormone increased 3H-thymidine incorporation and SM-C/IGF I release within all groups, and insulin release in the 16.7 mmol/l glucose and 2.7 mmol/l plus amino acid groups. The ability of growth hormone to increase 3H-thymidine incorporation in the presence of 16.7 mmol/l glucose, but not its action on insulin release, was partly inhibited by a monoclonal antibody against SM-C/IGF I (control cultures 100%; growth hormone alone 261±27%, mean±SEM; growth hormone+anti-SM-C/IGFI 179±21%; p<0.05, n=18). Growth hormone, but not 100 ng/ml SM-C/IGF I, increased insulin biosynthesis assessed as immunoprecipitable 3H-labelled insulin by 45%, but this was accompanied by a similar increase in overall protein synthesis. Similarly growth hormone, but not SM-C/IGF I caused a 75% increase in glucose oxidation by islets. Both growth hormone and SM-C/IGF I failed to increase the cellular uptake of α-aminoisobutyric acid or 3-O-methyl glucose over a 90 min period. The results suggest that while the stimulatory effect of growth hormone on islet cell insulin biosynthesis and release, glucose oxidation and general protein synthesis is probably direct, its action on B-cell replication is partly mediated by a paracrine release of SM-C/IGF I. This may provide a mechanism for increasing B-cell mass and consequently total insulin output during times of increased metabolic demands on insulin secretion.
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References
Cicchitti LF (1964) Growth hormone and mitoses in the islets of Langerhans of the rat. Acta Physiol Lat Am 14: 324–326
Martin JM, Åkerblom HK, Garay G (1968) Insulin secretion in rats with elevated levels of circulating growth hormone due to MtT-W15 tumor. Diabetes 17: 661–667
Peak GT, McKeel DW, Mariz IK, Jarett L, Daughaday WH (1969) Insulin storage and release in rats bearing growth hormone secreting tumors. Diabetes 18: 619–624
Pierlussi J, Pierlussi R, Ashcroft SJH (1980) Effects of growth hormone on insulin release in the rat. Diabetologia 19: 391–396
Parsons JA, Hartfel MA, Hegre OD, McEvoy RC (1983) Effects of MtTW15 mammasomatotropic tumors on pancreatic islet hormones. Diabetes 32: 67–74
Malaisse WJ, Malaisse-Lagae F, King S, Wright PH (1968) Effect of growth hormone on insulin secretion. Am J Physiol 215: 423–428
Schatz H, Abdel Rahman Y, Hinz M, Fehm HL, Nierle C, Pfeiffer EF (1973) Hypophysis and function of pancreatic islets. I. The influence of hypophysectomy on insulin secretion and biosynthesis of proinsulin and insulin in isolated pancreatic islets of rats. Diabetologia 9: 135–139
Parman AÜ (1975) Effects of hypophysectomy and short-term growth hormone replacement on insulin release from and glucose metabolism in isolated rat islets of Langerhans. J Endocrinol 67: 1–17
Pierlussi J, Pierlussi R, Ashcroft SJH (1982) Effects of hypophysectomy and growth hormone on cultured islets of Langerhans of the rat. Diabetologia 22: 134–137
Hellerström C, Swenne I (1985) Growth pattern of pancreatic islets in animals. In: Volk BW, Arquilla ER (eds) The diabetic pancreas. Plenum, New York, p 53–79
Van Wyk JJ (1984) The somatomedins: biological actions and physiological control mechanisms. In: Li CH (ed) Hormonal proteins and peptides, vol 12. Academic Press, New York, pp 81–96
Rabinovitch A, Quigley C, Rechler MM (1983) Growth hormone stimulates islet B-cell replication in neonatal rat pancreatic monolayer cultures. Diabetes 32: 307–312
Whittaker PJ, Taylor KW (1980) Direct effects of rat growth hormone on rat islet of Langerhans in tissue culture. Diabetologia 18: 323–328
Milner RDG, Hill DJ (1987) Interaction between endocrine and paracrine peptides in prenatal growth control. Eur J Paediatr 146: 113–122
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
Hill DJ, Frazer A, Swenne I, Wirdnam PK, Milner RDG (1987) Somatomedin-C in human fetal pancreas. Cellular localization and release during culture. Diabetes 36: 465–471
Romanus JA, Terrel JE, Yang YWH, Nissley SP, Rechler MM (1986) Insulin-like growth factor carrier proteins in neonatal and adult rat serum are immunologically different: demonstration using a new radioimmunoassay for the carrier protein from BRL-3A rat liver cells. Endocrinology 118: 1743–1758
Swenne I, Hill DJ, Strain AJ, Milner RDG (1987) Growth hormone regulation of somatomedin C/insulin-like growth factor I production and DNA replication in fetal rat islets in tissue culture. Diabetes 36: 288–294
Howell SL, Taylor KW (1968) Potassium ions and the secretion of insulin by islets of Langerhans incubated in vitro. Biochem J 108: 17–24
Swenne I, Bone AJ, Howell SL, Hellerström C (1980) Effects of glucose and amino acids on the biosynthesis of DNA and insulin in fetal rat islets maintained in tissue culture. Diabetes 29: 686–692
Russel WE, Van Wyk JJ, Pledger WJ (1984) Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci USA 81: 2389–2392
Kissane JM, Robins E (1958) The fluorometric measurement of deoxyribonucleic acid in animal tissues with special reference to the central nervous system. J Biol Chem 233: 184–188
Hinegardner RT (1971) An improved fluorometric assay for DNA. Anal Biochem 39: 197–201
Heding L (1972) Determination of total serum insulin (IRI) in insulin-treated diabetic patients. Diabetologia 8: 260–266
Hill DJ, Crace CJ, Fowler L, Holder AT, Milner RDG (1984) Cultured fetal rat myoblasts release peptide growth factors which are immunologically and biologically similar to somatomedin. J Cell Physiol 119: 349–358
Gey GO, Gey MK (1936) The maintenance of human normal cells and tumor cells in continous culture. I. Preliminary report: cultivation of mesoblastic tumours and normal tissue and notes on methods of cultivation. Am J Cancer 27: 45–76
Halban PA, Wollheim CB, Blondel B, Renold AE (1980) Longterm exposure of isolated pancreatic islets to mannoheptulose: evidence for insulin degradation in the B cell. Biochem Pharmacol 29: 2625–2633
Hellman B, Sehlin J, Täljedal I-B (1971) Transport of α-aminoisobutyric acid in mammalian pancreatic β-cells. Diabetologia 7: 256–265
Krebs HA, Henseleit K (1932) Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe-Seylers Z Physiol Chem 210: 33–66
Andersson A (1974) Long-term effects of glucose on insulin release and glucose oxidation by mouse pancreatic islets maintained in tissue culture. Biochem J 140: 377–382
Swenne I (1983) Effects of aging on the regenerative capacity of the pancreatic B-cell of the rat. Diabetes 32: 14–19
Swenne I (1984) The cell cycle and growth regulation of pancreatic B-cells. In: Larner J, Pohl S (eds) Methods in diabetes research. Laboratory methods, part B, vol 1. John Wiley, New York, pp 175–191
Edén S (1979) Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology 105: 555–560
Shin SH (1982) Detailed examination of episodic bursts of rGH secretion by high frequency blood sampling in normal male rats. Life Sci 31: 579–602
Clark RG, Carlsson LMS, Robinson ICAF (1987) Growth hormone secretory profiles in conscious female rats. J Endocrinol 114: 399–407
Nielsen JH (1982) Effects of growth hormone, prolactin, and placental lactogen on insulin content and release, and deoxyribonucleic acid synthesis in cultured pancreatic islets. Endocrinology 110: 600–605
Andersson I, Billig H, Fryklund L, Hansson H-A, Isaksson O, Isgaard J, Nilsson A, Rozell B, Skottner A, Stemme S (1986) Localization of IGF-I in adult rats. Immunohistochemical studies. Acta Physiol Scand 126: 311–312
Brown AL, Graham DE, Nissley SP, Hill DJ, Strain AJ, Rechler MM (1986) Developmental regulation of insulin-like growth factor II mRNA in different rat tissues. J Biol Chem 261: 13144–13150
Davidson MB (1987) Effect of growth hormone on carbohydrate and lipid metabolism. Endocrine Rev 8: 115–131
Hellman B, Sehlin J, Täljedal I-B (1971) Uptake of alanine, arginine, and leucine by mammalian pancreatic B-cells. Endocrinology 89: 1432–1439
Hellman B, Sehlin J, Täljedal I-B (1971) Stereospecific glucose uptake by pancreatic B-cells. Horm Metab Res 3: 219–220
Hellman B, Sehlin J, Täljedal I-B (1971) Evidence for mediated transport of glucose in mammalian pancreatic B-cells. Biochim Biophys Acta 241: 147–154
Hellman B, Sehlin J, Täljedal I-B (1972) Transport of L-leucine and D-leucine into pancreatic B-cells with reference to the mechanisms of amino-induced insulin release. Biochim Biophys Acta 266: 436–443
Whittaker PG, Taylor KW (1980) Direct effect of rat growth hormone on rat islets of Langerhans in tissue culture. Diabetologia 18: 323–328
Formby B, Ullrich A, Coussens L, Walker L, Petersen CM (1988) Growth hormone stimulates insulin gene expression in cultured human fetal pancreatic islets. Endocrinology 66: 1075–1079
Martin JM, Friesen H (1969) Effect of human placental lactogen on the isolated islets of Langerhans in vitro. Endocrinology 84: 619–621
Weir GC, Leahy JL, Bonner-Weir S (1986) Experimental reduction of B-cell mass: implications for the pathogenesis of diabetes. Diabetes Metab Rev 2: 125–161
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Swenne, I., Hill, D.J. Growth hormone regulation of DNA replication, but not insulin production, is partly mediated by somatomedin-C/insulin-like growth factor I in isolated pancreatic islets from adult rats. Diabetologia 32, 191–197 (1989). https://doi.org/10.1007/BF00265093
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DOI: https://doi.org/10.1007/BF00265093