Summary
The characteristics, progressivity and reversibility of the changes in glucose homeostasis brought about by chronic protein-calorie malnutrition were studied in the rat. Four-week-old male rats received a control diet (15% protein) or a low-protein diet (5% protein) until the age of 28 weeks. Other rats received the low-protein diet until 12–15 weeks, and then the control diet. In malnourished rats, fasting plasma glucose levels and both fasting and fed plasma insulin levels were lower than in control rats. At the age of 15 weeks, tolerance to oral glucose was slightly poorer, whereas tolerance to intravenous glucose was slightly better in rats receiving the low-protein diet than in control rats. During both tests the insulin response of malnourished rats was severely blunted. This inhibition largely exceeded the small decrease in their pancreatic insulin reserves. Similar results were obtained when the same test was repeated 9 weeks later. If the rats were transferred from a low-protein to a control diet for these 9 weeks, the changes in glucose tolerance were partially corrected, but the insulin response remained inhibited. Though hepatic glycogen stores were increased in malnourished rats, i. v. glucagon or arginine caused a smaller rise in plasma glucose levels than in control rats. The insulin response was also impaired and, unlike the glucose response, was not restored by 6 weeks on a control diet. The hypoglycaemia induced by intravenous insulin was more sustained in malnourished than in control rats, but this abnormality was corrected by refeeding a control diet for 6 weeks. The results thus show that chronic protein-calorie malnutrition in the rat severely impairs insulin secretion, but only mildly alters glucose tolerance, likely because of an associated high sensitivity to insulin. These changes do not aggravate with time and are only partially reversed by several weeks on a control diet.
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Kahn E, Wayburne S (1960) Hypoglycaemia in patients suffering from advanced protein malnutrition (kwashiorkor). Proc Nutr Soc S Afr 1: 21–23
Slone D, Taitz LS, Gilchrist GS (1961) Aspects of carbohydrate metabolism in kwashiorkor with special reference to spontaneous hypoglycemia. Br Med J 1: 32–64
Bowie MD (1964) Intravenous glucose tolerance in kwashiorkor and marasmus. S Afr Med J 38: 328–329
Baig HA, Edozien JC (1965) Carbohydrate metabolism in kwashiorkor. Lancet ii: 662–665
Heard CRC (1978) The effects of protein-energy malnutrition on blood glucose homeostasis. World Rev Nutr Diet 30: 107–147
Becker DJ (1983) The endocrine responses to protein calorie malnutrition. Annu Rev Nutr 3: 187–212
Rao RH (1984) The role of undernutrition in the pathogenesis of diabetes mellitus. Diabetes Care 6: 595–601
WHO Study Group on diabetes mellitus (1985) WHO Technical Report Series 727
Mohan V, Ramachandran A, Viswanathan M (1985) Tropical diabetes. In: Alberti KGMM, Krall LP (eds) The diabetes annual 1. Elsevier, Amsterdam, pp 82–92
Abu-Bakare A, Gill GV, Taylor R, Alberti KGMM (1986) Tropical or malnutrition-related diabetes: a real syndrome? Lancet i: 1135–1138
Heard CRC (1966) Effects of severe protein-calorie deficiency on the endocrine control of carbohydrate metabolism. Diabetes 15: 78–89
Heard CRC, Turner MR (1967) Glucose tolerance and related factors in dogs fed diets of suboptimal protein value. Diabetes 16: 96–107
Khardori R, Bajaj JS, Deo MG, Bansal DD (1980) Insulin secretion and carbohydrate metabolism in experimental protein malnutrition. J Endocrinol Invest 3: 273–278
Weinkove C, Weinkove EA, Pimstone BL (1976) Glucose tolerance and insulin release in malnourished rats. Clin Sci Mol Med 50: 153–163
Younoszai R, Dixit PK (1980) Decreased insulin secretion by isolated pancreatic islets from rats fed 4% protein diet. Proc Soc Exp Biol Med 164: 317–321
Levine LS, Wright PG, Marcus F (1983) Failure to secrete immunoreactive insulin by rats fed a low protein diet. Acta Endocrinol 102: 240–245
Dollet JM, Beck B, Villaume C, Max JP, Debry G (1985) Progressive adaptation of the endocrine pancreas during long-term protein deficiency in rats: effects on blood glucose homeostasis and on pancreatic insulin, glucagon and somatostatin concentrations. J Nutr 115: 1581–1588
Bhutani V, Kumar V, Misra UK (1975) Effect of inadequate dietary proteins on pancreatic insulin and cAMP levels in rats. Nutr Rep Int 32: 1413–1420
Lowry OH, Rosebrough NJ, Farr HL, Randall RF (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275
Hue L, Bontemps F, Hers HG (1975) The effect of glucose and of potassium ions on the interconversion of the two forms of glycogen phosphorylase and of glycogen synthetase in isolated rat liver preparations. Biochem J 152: 105–114
Phillips LS (1981) Nutrition, metabolism and growth. In: Daughaday WH (ed) Endocrine control of growth. Elsevier, New York, pp 121–173
Kalenga M, Henquin JC (1987) Alteration of lung mechanics by protein-calorie malnutrition in weaned rats. Respir Physiol 68: 29–39
Cherrington AD, Stevenson RW, Steiner KE, Davis MA, Myers SR, Adkins BA, Abumrad NN, Williams PE (1987) Insulin, glucagon and glucose as regulators of hepatic glucose uptake and production in vivo. Diabetes/Metabolism Reviews 3: 307–332
De Fronzo RA, Ferrannini E (1987) Regulation of hepatic glucose metabolism in humans. Diabetes/Metabolism Reviews 3: 415–459
Caddell JL, Goddard DR (1967) Studies in protein-calorie malnutrition. I: Chemical evidence for magnesium deficiency. N Engl J Med 276: 533–540
Legrand C, Okitolonda W, Pottier AM, Lederer J, Henquin JC (1987) Glucose homeostasis in magnesium-deficient rats. Metabolism 36: 160–164
Swenne I, Crace CJ, Milner RDG (1987) Persistent impairment of insulin secretory response to glucose in adult rats after limited period of protein-calorie malnutrition early in life. Diabetes 36: 454–458
Anthony LE, Faloona GR (1974) Plasma insulin and glucagon levels in protein-malnourished rats. Metabolism 23: 303–306
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Okitolonda, W., Brichard, S.M. & Henquin, J.C. Repercussions of chronic protein-calorie malnutrition on glucose homeostasis in the rat. Diabetologia 30, 946–951 (1987). https://doi.org/10.1007/BF00295879
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DOI: https://doi.org/10.1007/BF00295879