Impact of Maternal Diabetes Mellitus on the Thermoregulation of the Offspring

Abstract

Maternal diabetes mellitus (DM) can induce metabolic alterations in both newborn and adult offspring. It is believed that inadequate intrauterine conditions can impair thermogenic capacity of the offspring. The objective of the present study was to evaluate the effects of maternal DM on the offspring thermoregulation. DM was induced by streptozotocin injection (60 mg/g) in Wistar EPM-1 female rats. Control animals were injected with an equal volume of citrate buffer solution (pH 4.5). Fifteen days after confirmation of diabetes by glycaemia higher than 250 mg/dl, the rats were mated and the intercourse was confirmed by vaginal smear. Diabetic animals received daily 1 UI of insulin and control animals, an equivalent volume of saline. After delivery, 6 newborn females were randomly assigned to each mother in order to assure equivalent nutritional status during lactation during which body weight of the offspring was recorded daily. At weaning (28th day) the animals were transferred to individual metallic cages kept inside a chamber under a room temperature of 25°C. In the 60th day, half of the offspring was moved to a chamber at 5°C, remaining there until the 90th day. Four experimental groups were thus formed that were the offspring of control or diabetic dams acclimated at 25°C or 5°C. During the whole experimental period body weight and food intake were recorded and during the acclimation period energy balance was determined. When rats were 90 days-old, they were blood sampled and the carcasses prepared for calorimetric determination. At birth, weaning and 90 days of age, animals were killed for quantification of body fat, protein and water. Blood samples were collected and used to determine blood glucose and insulin. Offspring from diabetic dams showed lower body weight than controls throughout the whole experiment. No effect of maternal DM on energy balance of offspring acclimated at 25°C or at 5°C was observed. Nevertheless, as expected, cold induced an increase in energy intake and energy expenditure as well as a reduction in food efficiency, which was characterized by lower body weight and fat gain without change in body protein. Body composition was altered only at birth, when animals from diabetic mothers showed decreased body fat content and increased percentage of water in the carcass. Only at 90 days the rats from diabetic mothers showed higher glycaemia and lower blood insulin levels than controls suggesting delayed effects of maternal DM on the offspring. After weaning, rectal temperature of the animals was measured at 25°C and 5°C during 2 hours at time 0, 30, 60, 90, and 120 minutes. This parameter was determined at weaning and at 45, 60, 75, and 90 days of age. The results showed that the offspring from diabetic mothers not only had a delayed thermogenic capacity as shown by their inability to keep body temperature at 5°C until 90 days. It is, thus, suggested that maternal diabetes mellitus delayed thermoregulation of the offspring.

Key words

Maternal diabetes - thermoregulation - thermogenesis

References

• 1 Anderson S, Jung FF, Ingelfinger JR. Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations.  Am Physiol Soc. 1993;  34 F477-F486
• 2 Asakura H. Fetal and neonatal thermoregulation.  Nippon Med Sch. 2004;  71 360-370
• 3 Badawoud MH. Immunohistochemical and morphometric study of the effect of maternal diabetes on rat foetal pancreatic islets.  Folia Morphol (Warsz). 2003;  62 19-24
• 4 Barker DJP. The foetal ad infant origins of inequalities in health in Britain.  J Public Health Med. 1991;  13 64-68
• 5 Barr HG, McCracken KJ. High efficiency of energy utilization in “cafeteria”-and forced-fed rats kept at 29°C.  Br J Nutr. 1984;  51 379-387
• 6 Calvo R, Morreale de Escobar G, Escobar del Rey F, Obregon MJ. Maternal non-thyroidal illness and fetal thyroid hormone status, as studied in the streptozotocin-induced diabetes mellitus rat model.  Endocrinology. 1997;  138 1159-1169
• 7 Cowett RM, Schwartz R. The infant of the diabetic mother.  Pediatr Clin North Am. 1982;  29 1213-1231
• 8 Folch J, Lees M, Sloane-Stanley GHA. A simple method for isolation and purification of total lipids from animal tissue.  J Biol Chem. 1957;  226 497-509
• 9 Gasparo M, Milner RDG. The timing of fetal B cell hyperplasia in diabetic rat pregnancy.  Diabetologia. 1980;  19 54-57
• 10 Grishan FK. Calcium transport by basolateral membranes of diabetic rats.  Am J Clin Nutr. 1993;  58 209-214
• 11 Gordon CJ. Temperature Regulation in Laboratory Rodents. First Edition. 276p Cambridge University Press, Cambridge 1993
• 12 Harder T, Aerts L, Franke K, Van Bree R, Van Assche FA, Plagemann A. Pancreatic islet transplantation in diabetic pregnant rats prevents acquired malformation of the ventromedial hypothalamic nucleus in their offspring.  Neurosci Lett. 2001;  299 85-88
• 13 Hod M, Diamant YZ. The offspring of a diabetic mother - short and long range implications.  Isr J Med Sci. 1992;  28 81-86
• 14 Holemans K, Gerber RT, Meurrens K, Clerk F, Poston L, Van Assche FA. Streptozotocin diabetes in the rat induces cardiovascular dysfunction in adult offspring.  Diabetologia. 1999;  42 81-89
• 15 Jezek P. Possible physiological roles of mitochondrial uncoupling proteins - UCPn.  Int J Biochem Cell Biol. 2002;  34 1190-1206
• 16 Kervran A, Guillaume M, Jost A. The endocrine pancreas of the fetus from diabetic pregnant rat.  Diabetologia. 1978;  15 387-393
• 17 Le Blanc J. Man in the Cold. First Edition. p.192 Charles C. Thomas, Springfield 1975
• 18 Leshner AI, Litwin VA. A simple method for carcass analysis.  Physiol Behavior. 1972;  9 282-289
• 19 Lindsay RS, Hamilton BA, Calder AA, Johnstone FD, Walker JD. The relation of insulin, leptin and IGF-1 to birth-weight on offspring of women with type 1 diabetes.  Clin Endocrinol. 2004;  61 353-359
• 20 Luz J, Griggio MA, Vieira LV. Impact of maternal food restriction on cold-induced thermogenesis in the offspring.  Biol Neonate. 2003;  84 252-258
• 21 Merzouk H, Madani S, Chabane-Sari D, Prost J, Bouchenak M, Belleville J. Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrossomic offspring of rats with streptozotocin-induced diabetes.  Clin Science. 2000;  98 21-30
• 22 Merzouk H, Madani S, Boualga A, Prost J, Bouchenak M, Belleville J. Age related changes in cholesterol metabolism in macrossomic offspring of rats with streptozotocin-induced diabetes.  J Lipid Res. 2001;  42 1152-1159
• 23 Mostyn A, Pearce S, Stephenson T, Symonds ME. Hormonal and nutritional regulation of adipose tissue mitochondrial development and function in the newborn.  Exp Clin Endocrinol Diabetes. 2004;  112 2-9
• 24 Mulay S, Philip A, Solomon S. Influence of maternal diabetes on fetal rat development: alteration of insulin receptors in fetal liver and lung.  J Endocr. 1983;  98 401-410
• 25 Nazarova LA. The thermogenic characteristics in the early ontogeny of rats developing normally and under conditions of decreased uterine-placental blood circulation.  Ross Fiziol Zh Im I M Sechenova. 1993;  79 68-74
• 26 Nazarova LA, Petrova OP. Thermoregulatory reaction in the rabbit fetuses developing under the reduced uetro-placental blood flow.  Ross Fiziol Zh Im I M Sechenova. 1999;  85 1070-1074
• 27 Pillay D, Bailey E. Effects of insulin and maternal diabetes on fetal lipogenesis in the rat.  Enzyme. 1983;  29 126-130
• 28 Reitman ML, He Y, Gong DW. Thyroid hormone and other regulators of uncoupling proteins.  Int J Obes Relat Disord. 1999;  6 S56-S59
• 29 Rudge MVC, Calderon IMP, Ramos MD, Rodrigues MAM. Diabetes and experimental pregnancy in rats: course of maternal blood glucose levels and its repercussion on the blood glucose levels and pancreas of newborn pups.  Braz J Med Biol Res. 1995;  28 219-225
• 30 Satinoff E. Developmental aspects of behavioral and reflexive thermoregulation. In: Shair HN, Barr GA, Hofer M (eds). Developmental Psychobiology: New Methods and Changing Concepts. Oxford University Press, New York 1991: 169-188
• 31 Small M, Cameron A, Lunan CB, MacCuish AC. Macrosomia in pregnancy complicated by insulin-dependent diabetes mellitus.  Diabetes Care. 1987;  10 594-599
• 32 Tapanainen P, Leinonen E, Ruokonen A, Knip M. Leptin concentrations are elevated in newborn infants of diabetic mothers.  Horm Res. 2001;  55 185-190
• 33 Uvena-Celebrezze J, Catalano PM. The infant of the woman with gestational diabetes mellitus.  Clin Obstet Gynecol. 2000;  43 127-139
• 34 Wilker RE, Fleischman AR, Saenger P, Pan C, Surks MI. Thyroid hormone levels in diabetic mothers and their neonates.  Am J Perinatol. 1984;  1 259-262
• 35 Winer BJ. Statistical principles in experimental design. Second Edition. p. 907 Mc Graw-Hill New York 1971
• 36 Yamada R, Griggio MA, Luz J. Energy balance of pregnant diabetic rats.  Br J Nutr. 2002;  87 509-515
• 37 Zaninovich AA. Thyroid hormones, obesity and brown adipose tissue thermogenesis.  Medicina (B Aires). 2001;  61 597-602

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