ORIGINAL ARTICLE

JOP. J Pancreas (Online) 2008; 9(4):477-488.

Impaired Insulin Secretion in Perfused Pancreases Isolated from Offspring of Female Rats Fed a Low Protein Whey-Based Diet

Matthew PG Barnett1, Anthony RJ Phillips1,2, Patricia M Harris4, Garth JS Cooper1,3

1School of Biological Sciences, Faculty of Science; Departments of 2Surgery and 3Medicine, Faculty of Medical and Health Sciences, The University of Auckland. Auckland, New Zealand. 4AgResearch Limited, Grasslands Research Centre. Palmerston North, New Zealand

ABSTRACT

Context Insufficient maternal protein intake has been postulated to cause impaired fuel metabolism and diabetes mellitus in adult mammalian progeny, but the mechanism remains unclear.

Objective To investigate the effect of a maternal low protein whey-based diet during pregnancy and lactation on pancreatic function and skeletal muscle glucose metabolism in the offspring.

Animals Sprague-Dawley rats: 8 mothers and 46 offspring.

Design Female rats were fed throughout pregnancy and lactation with otherwise-complete isoenergetic diets sufficient (20% whey protein; control: n=3) or insufficient (5% whey protein; low-protein: n=5) in whey protein. From weaning all offspring ate control diet.

Main outcome measures Food intake and weight gain were measured for both mothers and offspring, and in vitro functional studies of endocrine pancreas and skeletal muscle were performed on offspring at 40 and 50 days of age, respectively.

Results Food intake (P=0.004) and weight gain (P=0.006) were lower in low protein than control mothers during early gestation. Offspring of low protein mothers had significant lower body weight from 5 to 15 days of age, although there was no significant difference in food consumption. Glucose, arginine- and glucose/arginine-stimulated insulin secretion from perfused pancreases isolated from low protein offspring were decreased by between 55 and 65% compared with control values. Studies in skeletal muscle demonstrated no difference in insulin sensitivity between the two groups.

Conclusions Dietary whey protein insufficiency in female rats during pregnancy and lactation can evoke major changes in insulin secretion in progeny, and these changes represent a persistent functional abnormality in the endocrine pancreas.

Full text: HTML format  PDF format

References

  1. Bertram CE, Hanson MA. Animal models and programming of the metabolic syndrome. Br Med Bull 2001; 60:103-21. [More details]

  2. Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull 2001; 60:5-20. [More details]

  3. Patel MS, Srinivasan M. Metabolic programming: causes and consequences. J Biol Chem 2002; 277:1629-32. [More details]

  4. Barker DJ, Martyn CN, Osmond C, Wield GA. Abnormal liver growth in utero and death from coronary heart disease. BMJ 1995; 310:703-4. [More details]

  5. Fall CH, Vijayakumar M, Barker DJ, Osmond C, Duggleby S. Weight in infancy and prevalence of coronary heart disease in adult life. BMJ 1995; 310:17-9. [More details]

  6. Barker DJ, Osmond C, Rodin I, Fall CH, Winter PD. Low weight gain in infancy and suicide in adult life. BMJ 1995; 311:1203. [More details]

  7. Barker DJ, Osmond C, Simmonds SJ, Wield GA. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 1993; 306:422-6. [More details]

  8. Godfrey KM, Barker DJ, Peace J, Cloke J, Osmond C. Relation of fingerprints and shape of the palm to fetal growth and adult blood pressure. BMJ 1993; 307:405-9. [More details]

  9. McCance RA, Widdowson EM. The determinants of growth and form. Proc R Soc Lond B Biol Sci 1974; 185:1-17. [More details]

  10. Ozanne SE, Olsen GS, Hansen LL, Tingey KJ, Nave BT, Wang CL, et al. Early growth restriction leads to down regulation of protein kinase C zeta and insulin resistance in skeletal muscle. J Endocrinol 2003; 177:235-41. [More details]

  11. Metges CC. Does dietary protein in early life affect the development of adiposity in mammals? J Nutr 2001; 131:2062-6. [More details]

  12. Ozanne SE, Dorling MW, Wang CL, Nave BT. Impaired PI 3-kinase activation in adipocytes from early growth-restricted male rats. Am J Physiol Endocrinol Metab 2001; 280:E534-9. [More details]

  13. Chamson-Reig A, Thyssen SM, Arany E, Hill DJ. Altered pancreatic morphology in the offspring of pregnant rats given reduced dietary protein is time and gender specific. J Endocrinol 2006; 191:83-92. [More details]

  14. Dumortier O, Blondeau B, Duvillié B, Reusens B, Bréant B, Remacle C. Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet. Diabetologia 2007; 50:2495-503. [More details]

  15. Snoeck A, Remacle C, Reusens B, Hoet JJ. Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biol Neonate 1990; 57:107-18. [More details]

  16. Hales CN. Fetal and infant origins of adult disease. J Clin Pathol 1997; 50:359. [More details]

  17. Sindayikengera S, Xia WS. Nutritional evaluation of caseins and whey proteins and their hydrolysates from Protamex. J Zhejiang Univ Sci B 2006; 7:90-8. [More details]

  18. Mardon J, Zangarelli A, Walrand S, Davicco MJ, Lebecque P, Demigné C, et al. Impact of energy and casein or whey protein intake on bone status in a rat model of age-related bone loss. Br J Nutr 2008; 99:764-72. [More details]

  19. Rogers AE. Nutrition. In: Baker HJ, Lindsey JR, Weisbroth SH (eds): Laboratory Rat, Volume I: Biology and Disease. New York, Academic Press, 1979, pp 123-52. [More details]

  20. Cherala G, Shapiro BH, D'mello AP. Two low protein diets differentially affect food consumption and reproductive performance in pregnant and lactating rats and long-term growth in their offspring. J Nutr 2006; 136:2827-33. [More details]

  21. Christie WW. Lipid Analysis: Isolation, Separation, Identification and Structural Analysis of Lipids. 3rd Ed. The Oily Press, Bridgwater, 2003. [More details]

  22. Blakeney AB, Mutton LL. A simple calorimetric method for the determination of sugars in fruit and vegetables. J Sci Food Agric 1980; 31:889-97. [More details]

  23. Koziol MJ. An evaluation of the alkaline p-hydroxybenzoic acid hydrazide procedure for the determination of reducing sugars. Anal Chim Acta 1981; 128:195-205. [More details]

  24. Cunniff P. Chapter 45, Vitamins and Other Nutrients, Method 982.30. AOAC international: Gaithersburg, Maryland, 1997; p 59-60. [More details]

  25. Crooker BA, Clark JH, Shanks RD. Effects of formaldehyde treated soybean meal on milk yield, milk composition, and nutrient digestibility in the dairy cow. J Dairy Sci 1983; 66:492-504. [More details]

  26. Lynch JM, Barbano DM, Fleming JR. Indirect and direct determination of the casein content of milk by Kjeldahl nitrogen analysis: collaborative study. J AOAC Int 1998; 81:763-74. [More details]

  27. Livesey G. A perspective on food energy standards for nutrition labelling. Br J Nutr 2001; 85:271-87. [More details]

  28. Livy DJ, Miller EK, Maier SE, West JR. Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus. Neurotoxicol Teratol 2003; 25:447-58. [More details]

  29. Qiang M, Wang MW, Elberger AJ. Second trimester prenatal alcohol exposure alters development of rat corpus callosum. Neurotoxicol Teratol 2002; 24:719-32. [More details]

  30. Donnelly CP, Trites AW, Kitts DD. Possible effects of pollock and herring on the growth and reproductive success of Steller sea lions (Eumetopias jubatus): insights from feeding experiments using an alternative animal model, Rattus norvegicus. Br J Nutr 2003; 89:71-82. [More details]

  31. Grodsky GM, Fanska RE. The in vitro perfused pancreas. Methods Enzymol 1975; 39:364-72. [More details]

  32. Gedulin B, Cooper GJ, Young AA. Amylin secretion from the perfused pancreas: dissociation from insulin and abnormal elevation in insulin-resistant diabetic rats. Biochem Biophys Res Commun 1991; 180:782-9. [More details]

  33. Hunter WM, Greenwood FC. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature 1962; 194:495-6. [More details]

  34. Petry CJ, Ozanne SE, Hales CN. Programming of intermediary metabolism. Mol Cell Endocrinol 2001; 185:81-91. [More details]

  35. Kanarek RB, Schoenfeld PM, Morgane PJ. Maternal malnutrition in the rat: effects on food intake and body weight. Physiol Behav 1986; 38:509-15. [More details]

  36. Arnold DL, Bryce FR, Clegg DJ, Cherry W, Tanner JR, Hayward S. Dosing via gavage or diet for reproduction studies: a pilot study using two fat-soluble compounds-hexachlorobenzene and aroclor 1254. Food Chem Toxicol 2000; 38:697-706. [More details]

  37. Shirley B. The food intake of rats during pregnancy and lactation. Lab Anim Sci 1984; 34:169-72. [More details]

  38. Latorraca MQ, Carneiro EM, Boschero AC, Mello MA. Protein deficiency during pregnancy and lactation impairs glucose-induced insulin secretion but increases the sensitivity to insulin in weaned rats. Br J Nutr 1998; 80:291-7. [More details]

  39. Nesher R, Cerasi E. Modeling phasic insulin release: immediate and time-dependent effects of glucose. Diabetes 2002; 51 Suppl 1:S53-9. [More details]

  40. Porte D Jr, Kahn SE. beta-cell dysfunction and failure in type 2 diabetes: potential mechanisms. Diabetes 2001; 50 Suppl 1:S160-3. [More details]

  41. Berney DM, Desai M, Palmer DJ, Greenwald S, Brown A, Hales CN, Berry CL. The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation. J Pathol 1997; 183:109-15. [More details]

  42. Dégano P, Silvestre RA, Salas M, Peiró E, Marco J. Amylin inhibits glucose-induced insulin secretion in a dose-dependent manner. Study in the perfused rat pancreas. Regul Pept 1993; 43:91-6. [More details]

  43. Rodriguez-Gallardo J, Silvestre RA, Salas M, Marco J. Rat amylin versus human amylin: effects on insulin secretion in the perfused rat pancreas. Med Sci Res 1995; 23:569-70. [More details]

  44. Hettiarachchi M, Chalkley S, Furler SM, Choong YS, Heller M, Cooper GJ, Kraegen EW. Rat amylin-(8-37) enhances insulin action and alters lipid metabolism in normal and insulin-resistant rats. Am J Physiol Endocrinol Metab 1997; 273:E859-67. [More details]

  45. Moura AS, Caldeira Filho JS, de Freitas Mathias PC, de Sá CC. Insulin secretion impairment and insulin sensitivity improvement in adult rats undernourished during early lactation. Res Commun Mol Pathol Pharmacol 1997; 96:179-92. [More details]

  46. de Souza Caldeira Filho J, Moura AS. Undernutrition during early lactation period induces metabolic imprinting leading to glucose homeostasis alteration in aged rats. Res Commun Mol Pathol Pharmacol 2000; 108:213-26. [More details]

  47. Lucas A, Baker BA, Desai M, Hales CN. Nutrition in pregnant or lactating rats programs lipid metabolism in the offspring. Br J Nutr 1996; 76:605-12. [More details]

Keywords Diabetes Mellitus, Type 2; Embryonic and Fetal Development; Pancreatic Hormones

Correspondence Matthew PG Barnett: matthew.barnett@agresearch.co.nz

JOP Home page