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Title: Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans

item KAPLAN, WALID - Baylor College Of Medicine
item SUNEHAG, AGNETA - Children'S Nutrition Research Center (CNRC)
item DAO, HARRY - Baylor College Of Medicine
item HAYMOND, MOREY - Children'S Nutrition Research Center (CNRC)

Submitted to: Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/7/2008
Publication Date: 6/9/2008
Citation: Kaplan, W., Sunehag, A.L., Dao, H., Haymond, M.W. 2008. Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans Metabolism. 57(6):725-732.

Interpretive Summary: We are studying the way that glucose, a form of sugar, is produced in the body. Glucose production is a very complicated process called "gluconeogenesis". We are interested in glucose production because we are trying to understand the disease of diabetes. Diabetic people have too much sugar stored in the body because their bodies cannot make enough of the hormone "insulin" to use it. In particular, we are interested in glucose production in women who are breastfeeding. Women who are breastfeeding, or "lactating", are good subjects for our experiments because we can study the content of the milk, and how much milk they produce, under different conditions. In our experiments we show that after a short while of not eating (fasting) lactating women produce more glucose, but fasting does not seem to affect the process of gluconeogenesis even though the amount of insulin present is low. We also looked at the effects of human growth hormone on the production of glucose. This hormone increased milk production in the lactating women, and also produced "insulin-like growth factor". The results of our experiments suggest that we need to think again about the way that insulin affects gluconeogenesis.

Technical Abstract: After a short-term fast, lactating women have increased rates of glucose production but not gluconeogenesis (GNG) despite relative hypoinsulinemia. We explored the effects of non-insulin-dependent increase in glucose utilization and recombinant human growth hormone (rhGH) on glucose production, glycogenolysis, and GNG in both the fed and overnight-fasted condition. Six controls and 7 lactating women were studied twice, in random order, after 7 days of saline or rhGH. Glucose kinetics and GNG were measured using [U-(13)C]glucose mass isotopomer distribution analysis. The rhGH increased milk production in the lactating women and insulin-like growth factor (IGF) in both groups. Glycogenolysis and GNG were higher in fasting lactating women than controls after either saline or rhGH (P < .05). After rhGH administration, GNG remained higher (P < .02) in the lactating women than controls. Gluconeogenesis was not suppressed in either group during 5 hours of continuous meal ingestion, despite a 5-fold increase in plasma insulin. Lactating women had similar glucose but lower insulin and C-peptide concentrations than controls after both rhGH and saline treatment (P < .01), although rhGH decreased (P < .01) insulin sensitivity in both groups (P < .05). Gluconeogenesis is not affected by short-term increases in insulin and/or rhGH, which suggests a fundamental rethinking of the role of insulin in acutely regulating GNG.