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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose tolerance deteriorates in human pregnancy, but about 97-98% of all pregnant women retain a normal glucose tolerance and only 2-3% develop gestational diabetes. The data reviewed show that the diabetogenicity of pregnancy is not due to diminished secretion of insulin or disproportional secretion of proinsulin or glucagon, nor is an increased insulin degradation involved. Only quantitative differences in insulin secretion have been observed between normal pregnant women and women with gestational diabetes. The insulin responses to an oral glucose load or a test meal are thus lower in gestational diabetic women than in normal pregnant women, despite significantly higher plasma glucose concentrations in the gestational diabetics. Also the insulin responses to intravenous glucose injections or infusions are abnormal in gestational diabetics when compared with normal pregnant women, a difference which is still detectable for some time after the completion of pregnancy in at least a fraction of gestational diabetic women. There is thus ample evidence that the diabetogenicity of pregnancy is related to a pronounced peripheral resistance to insulin. The resistance is of a similar magnitude in normal pregnant women and women with gestational diabetes, and it does not seem to be caused by significant alterations in insulin receptor binding to target tissues. The insulin resistance of the whole body is increased to about three times that seen in the non-pregnant state. The increased resistance is caused by post-insulin receptor events and is probably brought about by the cellular effects of the increased plasma levels of one or more of the pregnancy-associated hormones and free cortisol. There is evidence that the resistance is predominantly located to the muscle tissue, where significant reductions in certain key enzymes in glucose and lipid metabolism have been demonstrated. Published evidence points to a similar degree of insulin resistance in normal pregnant women and normal weight women with gestational diabetes. Most normal pregnant women are able to counteract the peripheral resistance by a significant augmentation of their basal and nutrient-stimulated insulin secretion. However, a few (2-3%) of the women do not appear to have the capability to produce a sufficiently large increase in insulin secretion and hence cannot overcome the peripheral resistance. These are the women who become glucose intolerant to such an extent that the diagnostic criteria for gestational diabetes are fulfilled.
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PMID:Aetiology of gestational diabetes. 195 14

The relationship between the deterioration of glucose tolerance and plasma prolactin (PRL) levels was investigated in 15 normal pregnant women and in 15 women with gestational diabetes mellitus. Oral glucose tolerance tests were performed in late pregnancy and postpartum, and the insulin, glucagon, and PRL responses were measured. In late pregnancy the gestational diabetics revealed significantly elevated fasting glucose levels compared with the normal pregnant women and after the glucose challenge their insulin responses were significantly diminished and the suppression of glucagon less pronounced. These differences in glucose metabolism were markedly reduced early postpartum. There was no difference in basal PRL concentrations between the two groups neither in pregnancy nor postpartum. The PRL levels were not altered during the oral glucose tolerance tests and no correlation between the deterioration of glucose tolerance and the PRL concentrations could be demonstrated in either group. These results indicate that abnormal PRL levels are not of pathophysiologic importance for the development of gestational diabetes mellitus.
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PMID:Prolactin and glucose tolerance in normal and gestational diabetic pregnancy. 351 13

Glucose tolerance deteriorates in normal human pregnancy but 99% of all pregnant women retain normal glucose tolerance whereas the remaining 1% develop abnormal glucose tolerance and are designated gestational diabetics. The possibility that glucose tolerance deteriorates in pregnancy because of diabetes-like changes in the secretory function of the endocrine pancreas has been investigated in gestational diabetics and healthy controls. Even though the insulin responses to oral glucose and mixed meals are equally large in gestational diabetics and normal pregnant women, the insulin responses of the gestational diabetics differ in two pertinent ways from those of the normals. First, a delayed insulin response is frequently seen, and second, the insulin response per unit of glycaemic stimulus (the 'insulinogenic index') is normally significantly lower than that of the normal pregnant women. Diabetes-like changes in the secretion of glucagon are not seen in neither group. Insulin degradation is unaffected by pregnancy and the proinsulin share of the total plasma insulin immunoreactivity does not increase in pregnancy. It is therefore likely that the main reason for the diabetogenicity of pregnancy is insulin resistance. Most pregnant women are able to increase their insulin secretion and thus overcome the resistance. Some pregnant women do, however, seem to have a more limited insulin secretory capacity which eventually may lead to the development of gestational diabetes.
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PMID:Endocrine pancreatic function in women with gestational diabetes. 353 65

In order to better understand the role of A- and B-cell function in diabetic pregnancy, we studied four groups of pregnant women at week 34-36 of gestation. Seventeen were healthy controls (C), 24 had gestational diabetes (GD), 16 had type 2 diabetes (NIDD) and 37 had type 1 diabetes (IDD). At times -20, 0, 20, 30, 45, 60, 90 and 120 min from the beginning of a 30 min infusion of 30 g of arginine intravenously, plasma glucose, glucagon (IRG) and C-peptide (CPR) were measured. Plasma glucose was higher in diabetic than in control subjects. IRG values were also higher in the GD and the NIDD women. CPR values were similar to, or slightly higher than control values in the GD and the NIDD and were much lower in the IDD women. All three variables increased during the arginine infusion in all groups, with the exception that CPR remained unchanged in the IDD. The CPR/IRG molar ratio was similar in control, GD and NIDD women; in the IDD, it was much smaller than in the other groups and was not affected by arginine. In all the diabetic patients, IRG was negatively correlated with the maternal weight gain and in the IDD IRG was positively correlated with the increase in the insulin need and with the CPR levels. In conclusion diabetes appeared to enhance the A-cell function also in pregnancy, possibly impairing the 'facilitated anabolism' and stressing the 'accelerated starvation' which are typical of normal pregnancy. Glucagon was confirmed as one possible determinant of the insulin resistance seen in diabetic pregnancy.
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PMID:Endocrine pancreatic function in insulin-dependent diabetic pregnant women. 353 67

To evaluate the metabolic basis of gestational glucose intolerance (gestational diabetes), the response of normal pregnant women (N=6) and lean (N=23), and obese (N=12) gestational diabetics to the physiologic challenge of a 400-kcal mixed meal breakfast tolerance test was studied. Obese patients with gestational diabetes were more hyperglycemic than the lean gestational diabetics in both the fasting and postprandial periods. Women with gestational diabetes had a more prolonged glycemic response and a later insulin response to meal stimulation than normal control subjects. Fasting and postprandial insulin levels were higher in the obese gestational diabetes group, whereas those of lean subjects fell below the values of the control group. The percent specific binding of insulin to red blood cell receptors was lower in both gestational diabetes groups than in control subjects, with the most marked decrease in the obese group. Mean fasting plasma levels of total cholesterol and triglyceride and plasma glucagon levels during the meal tolerance test were not significantly different among the three groups. Obese gestational diabetics had significantly larger infants and placentas than lean gestational diabetics. These findings, taken together, suggest that the pathophysiology of gestational diabetes differs between obese and lean patients. Lean gestational diabetics appear to develop glucose intolerance on the basis of relative insulin deficiency in contrast to obese gestational diabetics who manifest glucose intolerance characterized by insulin resistance, hyperinsulinemia, and decreased insulin binding to red blood cell receptors.
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PMID:Demonstration of heterogeneity in gestational diabetes by a 400-kcal breakfast meal tolerance test. 388 Aug 78

In pregnancy, several physiologic changes take place, the sum of which tends to reset the glucose homeostasis in the direction of diabetes. About 1-2% of all pregnant women develop an abnormal glucose tolerance in pregnancy, but most often glucose tolerance returns to normal postpartum. This condition is called gestational diabetes mellitus (GDM). The possibility that glucose tolerance deteriorates in pregnancy because of diabetes-like changes in the secretory function of the endocrine pancreas has been investigated in healthy controls and in normal-weight gestational diabetic subjects. The insulin responses to oral glucose and mixed meals are equally large in these two groups, but the insulin response per unit of glycemic stimulus is significantly lower in the gestational diabetic subjects than in the controls. Diabetes-like changes in glucagon secretion are not observed in either group. Insulin degradation is unaffected by human pregnancy and the proinsulin share of the total plasma insulin immunoreactivity does not increase in pregnancy. Insulin receptor binding to monocytes from normal pregnant women is increased in midpregnancy but is significantly decreased in late pregnancy. No difference in insulin binding (at tracer insulin concentration) to monocytes from healthy pregnant controls and gestational diabetic subjects is found. The insulin concentration necessary to reduce tracer insulin binding by 50% (ID50) is lower in the gestational diabetic subjects diagnosed in late pregnancy than in the pregnant controls. Together, these findings indicate that the number of insulin receptors on monocytes is decreased in GDM at this stage of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Etiology and pathophysiology of gestational diabetes mellitus. 388 44

Glucose tolerance is impaired in normal pregnancy and in approximately 1% of all pregnant women gestational diabetes develop. The present paper reviews the pathogenesis of these changes based on the modifications of glucagon and insulin secretion and action. Fasting plasma glucagon levels are increased in pregnancy in normal and gestational diabetic women. After glucose ingestion or infusion the suppression of glucagon levels is enhanced in pregnancy whereas the response to protein is unaffected. The results indicate that the changes in glucagon secretion in pregnancy are secondary to altered plasma glucose levels. In all women the fasting plasma insulin levels and the glucose--or protein--induced insulin response is increased in pregnancy. The responses are similar in normal women and normal weight gestational diabetics whereas greater responses are seen in overweight gestational diabetics. Morphological and physiological animal studies demonstrate B-cell hypertrophy and hyperplasia and increased insulin secretory responsiveness in pregnancy, which is corroborated by human studies showing an almost 4-fold increase in insulin response when the same glycemic stimulus is applied in pregnancy and postpartum. The increased insulin responsiveness seems to be caused by pregnancy-related changes in the secretion of progesterone, estradiol, human placental lactogen (hPL) and prolactin. However, the increased insulin levels are unable to maintain normal glucose tolerance and pregnancy, thus, is a state of insulin resistance. Receptor studies yield diverging results, but indicate a postreceptor defect in insulin action in pregnancy. This may be caused by the increased cortisol levels in pregnancy, as significant positive correlations between increases in cortisol levels and the decreases in glucose tolerance have been established in normal pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:On the decrease of glucose tolerance in pregnancy. A review. 390 79

The effect of a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) on glucose tolerance, plasma insulin and glucagon responses to glucose, fasting plasma cortisol, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very--low-density lipoprotein cholesterol was investigated in 16 women with previous gestational diabetes and in 19 normal women. Investigations were performed prior to the hormonal intake and after treatment for 2 and 6 months. Before treatment, the women with previous gestational diabetes had significantly elevated fasting glucose (p less than 0.05) and impaired glucose tolerance (p less than 0.05) when compared to those of the healthy control subjects. The glucose, insulin, and glucagon responses to oral glucose remained unchanged during the treatment period. Plasma cortisol increased in both groups (p less than 0.05) whereas plasma triglycerides increased in the control subjects only (p less than 0.05). Plasma free fatty acids, lipoproteins, and high-density lipoprotein cholesterol/total cholesterol ratio remained unchanged in both groups. The results suggest that a low-dose triphasic oral contraceptive (ethinyl estradiol and levonorgestrel) is suitable as contraception even in women with a previous deterioration of glucose tolerance during pregnancy.
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PMID:Triphasic oral contraception: metabolic effects in normal women and those with previous gestational diabetes. 393 51

In normal and diabetic pregnancies, the placenta functions as a complex endocrine gland that modulates all classes of maternal nutrients to the fetus. The metabolic alterations of normal pregnancy are diabetogenic and associated with modest resistance to endogenous insulin. Pregnant women with carbohydrate intolerance represent three metabolically heterogeneous groups: type I (insulin-dependent), type II (non-insulin-dependent), and gestational diabetes. Patients with type I diabetes are at risk for ketosis and require replacement therapy because of a deficient production of insulin. They have decreased 24-hour, around-the-clock levels of C-peptide and glucagon, and lower nocturnal cortisol values and higher 24-hour prolactin levels than those of women with type II diabetes. Type II pregnant diabetic patients are not prone to ketosis and are more resistant to endogenous and exogenous insulin. They have higher fasting and meal-stimulated levels of C-peptide, accentuated fasting hypertriglyceridemia, and significantly lower high-density lipoprotein cholesterol levels than those of normal or type I women. In gestational diabetes, the metabolic stress of pregnancy evokes reversible hyperglycemia which may be associated with either a surfeit or a deficiency of insulin. These metabolic differences among diabetic pregnant women could have implications for placental structure and function that might influence fetal growth.
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PMID:Alterations of maternal metabolism in normal and diabetic pregnancies: differences in insulin-dependent, non-insulin-dependent, and gestational diabetes. 634 40

To study whether gestational diabetes is the result of abnormal endocrine pancreatic adaptation to pregnancy, alpha- and beta-cell sensitivity to glucose was determined during pregnancy and post partum in seven women of normal weight who had gestational diabetes. Glucose was infused intravenously in quantities producing similar increases in plasma glucose in pregnancy and post partum, and the plasma glucose curves obtained closely resembled those found during an oral glucose tolerance test. The insulin response to the infusion was 3.5 times greater in pregnancy (P less than .02), whereas glucagon was suppressed similarly in pregnancy and post partum. These findings resemble previous ones in normal women. It is concluded that pancreatic alpha and beta cells adapt similarly to pregnancy in women with gestational diabetes and in normal women.
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PMID:Endocrine pancreatic sensitivity to glucose in women with gestational diabetes. 634 12


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