The overall goal of this research program is to understand the interactions between maternal metabolism and lactation in humans. Animal work has shown that food deprivation profoundly depresses the rate of milk production in both ruminants and rodents. Conversely lactation itself alters systemic glucose and lipid homeostatic mechanisms to ensure a flux of substrate to the mammary gland. The hormonal and metabolic signals mediating both types of effect are not well understood. Human research in this area has been limited to comprehensive nutritional studies of lactation. While providing much valuable information such studies do not allow investigation of mechanisms. We propose a set of experimental studies which should allow us to: 1. determine whether the supply of glucose to the mammary alveolar cell is limiting for milk synthesis in lactating women. 2. determine whether insulin plays a role in regulating glucose entry into the mammary gland, lactose synthesis or fatty acid synthesis by the mammary gland. 3. determine the effects of acute fasting on milk secretion and metabolic parameters in lactating women. 4. examine systemic glucose metabolism in lactating women, comparing their responses to a glucose load and to insulin infusion during full lactation, partial lactation and post lactation. 5. examine the role of prolactin in the acute regulation of milk secretion and in the metabolic responses to lactation in order to determine whether this hormone plays a critical role in the interaction between metabolism and lactation. 6. examine the appearance of lipoprotein lipase into milk in order to determine the relationship between the secretion of long chain fatty acids and the secretion of this enzyme. Our experimental paradigm allows us to use frequent emptying of the breast to measure milk secretion in the fasting state and during glucose clamp studies. This paradigm allows rigorous control of blood glucose during experimental manipulation of such hormones as insulin and prolactin. It thus provides a rigorous experimental framework for examination of the effects of glucose, insulin, and prolactin on milk secretion and of the effects of lactation on maternal metabolism.
| Schwertfeger, Kathryn L; McManaman, James L; Palmer, Carol A et al. (2003) Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation. J Lipid Res 44:1100-12 |
| McManaman, James L; Neville, Margaret C (2003) Mammary physiology and milk secretion. Adv Drug Deliv Rev 55:629-41 |
| Neville, M C; Morton, J; Umemura, S (2001) Lactogenesis. The transition from pregnancy to lactation. Pediatr Clin North Am 48:35-52 |
| Neville, M C (2001) Anatomy and physiology of lactation. Pediatr Clin North Am 48:13-34 |
| Neville, M C (1999) Physiology of lactation. Clin Perinatol 26:251-79, v |
| Toddywalla, V S; Kari, F W; Neville, M C (1997) Active transport of nitrofurantoin across a mouse mammary epithelial monolayer. J Pharmacol Exp Ther 280:669-76 |
| Jensen, D R; Gavigan, S; Sawicki, V et al. (1994) Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the lactating mouse. Biochem J 298 ( Pt 2):321-7 |
| Neville, M C; Sawicki, V S; Hay Jr, W W (1993) Effects of fasting, elevated plasma glucose and plasma insulin concentrations on milk secretion in women. J Endocrinol 139:165-73 |
| Neville, M C; Waxman, L J; Jensen, D et al. (1991) Lipoprotein lipase in human milk: compartmentalization and effect of fasting, insulin, and glucose. J Lipid Res 32:251-7 |
| Jensen, D R; Bessesen, D H; Etienne, J et al. (1991) Distribution and source of lipoprotein lipase in mouse mammary gland. J Lipid Res 32:733-42 |
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