206 Horm. Metab. Res. 9 (1977) 206-209

© Georg Thieme Verlag Stuttgart

Effect of Pregnancy on the Glucagon Response to Protein Ingestion C. Kühl, P. Hornnes and J.G. Klebe Department of Internal Medicine T, Bispebjerg Hospital and Department of Gynaecology and Obstetrics, Oeresundshospitalet, University of Copenhagen, Copenhagen, Denmark

Plasma glucose, insulin and glucagon concentrations were measured before and after the ingestion of a protein-rich meal in 11 heaJthy pregnant women in the last trimester of pregnancy, and again in the same subjects postpartum. Compared to postpartum, basal levels of plasma glucose were lower in late pregnancy whereas basal insulin and glucagon concentrations were both enhanced. After the meal, insulin and glucagon concentrations in plasma increased in gestation as weil as postpartum. Plasma glucose increased slightly in pregnancy but remained unchanged postpartum. The mean insulin response to the meal was unaffected by pregnancy whereas that of glucagon was reduced. Thus following protein ingestion, plasma glucose rose in pregnancy in spite of unchanged levels of insulin and depressed levels of glucagon. Favouring anabolism, the reduced glucagon response to protein ingestion in pregnancy fits in the concept of 'facilitated anabolism' in late pregnancy and, mareover, it !end further support to the idea that changes in glucagon secretion per se are not involved in the pathogenesis of the diabetogenicity of pregnancy. Key-Words: Glucagon - Insulin - Blood Glucose - Human Pregnancy

Introduction It has been weil documented that the tolerance to oral glucose decreases in pregnancy in spite of elevated levels of serum insulin (Bleicher, 0 'Sullivan and Freinkel 1964, Kalkhoff, Sehaleh, Walker, Beck, Kipnis and Daughaday 1964, Lind, Billewicz and Brown 1973, Kühl 1975). The possibility that abnormal secretion of glucagon might be involved in this diabetogenicity of pregnancy has recently been investigated (Daniel, Metzger, Freinkel, Unger and Nizan 1974, Luyckx. Gerard, Gaspard and Lefebvre 1975, Kühl and Holst 1976). Even though plasma glucagon levels were elevated in late pregnancy. plasma insulin was on a molar basis even more elevated and the molar insulin-to-glucagon ratio was hence increased (Kühl and Holst 1976). In contrast, this ratio is diminished in diabetes (Unger 1971, Unger and Orei 1975). Furthermore, following an oral or intravenous glucose load plasma glucagon concentration decreased more in pregnancy than postparturn (Daniel, Metzger, Freinkel, FalooM, Unger and Nizan 1974, Luyckx, Gerard. Gaspard and Lefebvre 1975, Kühl and Holst 1976) a finding which contrasts the lack of suppressibility of glucagon which has been reported in diabetes (Unger, Aguilar-Parada, Müller Received: 20 Apr. 1976

Accepted: 28 Sept. 1976

and Ei&entraut 1970, Buchanan and McCarrollI972). Therefore, SO far, glucagon does not seem to be involved in the pathogenesis of the decreased to1erance to glucose in pregnancy.

The present investigation was initiated in order to elucidate further the secretion of glucagon in normal pregnancy. For this purpose plasma levels of glucagon, insulin and glucose were measured after the ingestion of a protein-rich meal in normal women in late pregnancy and postpartum.

Materials and Methods Subjects Eleven healthy, nonobese, aglucosuric, fern ale volunteers with normal basal blood glucose concentrations and aged 19-26 (mean 21.9) years were studied twice: hetween the 33rd and 39th week of gestation, and again 4-10 weeks postpartum. Prior to the actual pregnancy all volunteers were within 10% of their ideal body weight (Natvig 1956), and none had a family history of diabetes. The average parity was 0.2 (range: 0-1). Each wo man gave birth to a healthy infant of normal birth weight (mean: 3427 g; range: 29004300 g) at tenn. Informed consent was obtained from all subjects. Investigative procedure All subjects were instructed to take a diet containing at least 300 gm of carbohydrate for three days before testings. All tests were performed in the morning after a 10-12 hour fast and abstinence from smoking. Immediately upon arrival an intravenous cannula was inserted into an antecubital vein. After a 20 minutes rest, each subject ate a standardized protein meal consisting of 150 gm of tenderioin heef, caulitlower and gravy. The meal was ingested in a maximum of 20 minutes and contained approximately 35 gm of protein, 13 gm of lipid and 9 gm of carbohydrate. Each person was allowed 250 ml of drinking water with the meal. Blood sampies were drawn 10 and 5 minutes before (fasting values) and 20,40,60,90, 120, 150 and 180 minutes after start of the meal. Blood was drawn into chilled heparin tubes, containing in addition TrasylolQi) 500 KIV per ml of blood. Within 30 minutes tubes were centrifugated at 4 0 C and the plasma subsequently pipetted into plastic tubes and stored at - 25 0 C until assayed.

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Summary

Laboratory analyses and calculations Plasma was assayed for glucose on a Technicon Auto Analyzer by a glucose oxidase method (Trinder 1969) and for insulin by radioimmunoassay (Oerskov 1967). Glucagon concentration was determined in alcohol extracted (Heding 1971) plasma by radioimmunoassay (Holst and Aasted 1974). The antiserum used (4317) is highly specific for pancreatic glucagon, crossreacting less than 0.1 % with high concentrations of human gut glucagon immunoreactivity (Holst and Rehfeld 197 5). Standards were highly purified porcine glucago n

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Pregnancy and Glucagon Response to Protein Ingestion Table 1 Plasma. glu~ose. insulin and gluc

Effect of pregnancy on the glucagon response to protein ingestion.

206 Horm. Metab. Res. 9 (1977) 206-209 © Georg Thieme Verlag Stuttgart Effect of Pregnancy on the Glucagon Response to Protein Ingestion C. Kühl, P...
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