Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a constant intravenous infusion technique we have measured in vivo insulin resistance in 17 normal subjects, five patients with chemical diabetes, and 13 non-ketotic diabetic patients with fasting hyperglycaemia (FBS greater than 120 mg/100 ml). All of the diabetic patients were non-obese. The results demonstrated that the diabetic patients were insulin resistant compared to normals and that the degree of insulin resistance was greater the more severe the diabetes. No differences in plasma glucagon levels were found among the different groups during the infusion studies. These results demonstrate that non-obese, non-ketotic diabetic patients are insulin resistant and that abnormalities in plasma glucagon concentrations do not account for this insulin resistance.
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PMID:Does glucagon play a role in the insulin resistance of patients with adult non-ketotic diabetes? 91 24

We experienced a chronic alcoholic patient in whom a large intake of alcohol led to the development of frank clinical diabetes, and glucose intolerance and insulin deficiency improved perfectly following abstinence from alcohol. The patient was a 31-year-old male with no diabetes among his relatives. He was a heavy drinker since 12 years, and especially had a large intake of alcohol from Dec. 25 '84 to Jan. 3 '85. From the end of Jan. 1985 he complained of thirst, polydipsia, polyuria and body weight loss from 94 to 69 Kg. On June 25 1985 he admitted for the treatment of diabetes and had abstinence from alcohol. The blood glucose and HbA1 levels were 291 mg/dl and 14.7%, respectively on admission. His 75 g OGTT was diabetic in type and serum insulin response to glucose decreased markedly. Liver function tests were normal, and islet cell antibody was negative. Blood adrenaline, noradrenaline, growth hormone, glucagon, cortisol, T3 and T4 levels were normal. FBS, HbA1 and 75 g OGTT recovered to normal by dietary treatment (1800 kcal) with oral hypoglycemic agents for 8 weeks. This case report suggests that the cause of alcohol-induced diabetes is probably due to impairment of insulin secretion by either alcohol itself or alcohol metabolites.
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PMID:[A chronic alcoholic patient with the development of frank diabetes after heavy drinking and perfect improvement following abstinence from alcohol]. 152 26

In untreated primary cultures of neonatal rat liver kept in high-calcium (1.8 mmol/l), foetal bovine serum (10% v/v)- containing minimal essential medium (FBS-MEM), the absolute numbers of hepatocytes did not change between day 4 and day 9 because ongoing cell loss was counterbalanced by proliferation of a discrete sub-population of the cells. By contrast, the number of stromal cells increased linearly with time. Growth of hepatocytes and stromal cells was differently affected by the daily addition, between day 4 and day 8 of culture, of fresh medium to which peptide mitogen(s) in concentrations ranging from 10(-14) to 10(-8) mol/l had been added. Epidermal growth factor/urogastrone (EGF/URO) with or without equimolar mixtures of glucagon and insulin, induced first hyperplasia of hepatocytes and stromal cells and then apopotosis (degeneration and death) of the progeny of the stimulated cells. By contrast, equimolar mixtures of glucagon and insulin caused a progressive increase in the number of hepatocytes and stromal cells unbalanced by any increase in cell death. At subphysiological concentrations glucagon, in synergism with EGF/URO and/or some other unknown heat-stable component of serum, acted as a trophic factor for hepatocytes. By contrast, insulin alone did not enhance growth of hepatocytes, but rather blocked the mitogenic effects of EGF/URO. The three hormones exerted neither mitogenic nor apoptotic effects when administered in a low calcium (0.01 mmol/l) FBS-MEM medium. These results reveal that EGF/URO may control the size of cell populations in neonatal liver by calcium-dependent mechanisms that make it unlikely to be a promoter of hepatocyte tumours. They also show that glucagon acts as a positive trophic regulator for hepatocytes.
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PMID:Growth stimulation and apoptosis induced in cultures of neonatal rat liver cells by repeated exposures to epidermal growth factor/urogastrone with or without associated pancreatic hormones. 353 Apr 89

A single exposure to a low concentration (10-10 mol/L) of tumor promoters (like 12-0-tetradecanoylphorbol-13-acetate (TPA), phenobarbital, and nafenopin) or of hormones (as epidermal growth factor (EGF), glucagon and insulin) or of drugs (like imidazole and indomethacin) stimulated the 24-h flow into DNA synthesis and mitosis of primary neonatal rat hepatocytes incubated in high-calcium (1.8 mmol/L) Eagle's MEM-FBS medium. However, only tumor promoters acted as enhancers of hepatocytic DNA synthesis when a low-calcium (0.1 mmol/L) FBS-MEM medium was used. The tumor promoters' activity was completely suppressed by the simultaneous (or nearly such) addition of low doses (from 25.0 to .25 micrograms/ml; activity, from 100 to 1.0 unit/ml) of exogenous bovine liver Cu,Zn-superoxide dismutase (SOD), whatever the medium's calcium concentration. By contrast, SOD did not inhibit the growth stimulation elicited by hormones and drugs in hepatocytes exposed to the high-calcium FBS-MEM medium. Moreover, several tumor promoters (namely TPA, phenobarbital, nafenopin, saccharin, teleocidin, benzoyl peroxide, BHT, DDT, lindane, clofibrate, and melittin) stimulated DNA synthesis even when the hepatocytes were incubated in the serumless HiWoBa2000 medium, whatever its calcium concentration. In this synthetic medium, the tumor promoter's stimulatory activity was again completely written off by the simultaneous administration of exogenous (superoxide dismunate) SOD. These results disclose the existence of two quite different mechanisms by which neonatal rat hepatocyte growth can be stimulated: (i) the physiological-pharmacological extracellular calcium-dependent SOD-insensitive machinery, mediating the effects of EGF, glucagon, insulin, imidazole, and indomethacin; and (ii) the pathological extracellular calcium-independent SOD-suppressible mechanism operated by agents belonging to the tumor promoters class and involving, as a critical step, the generation of superoxide anions at the surface of the hepatocyte's plasma membrane. The present results also indicate that primary cultures of neonatal rat hepatocytes may constitute a useful tool for promptly and safely identifying compounds endowed with tumor promoters' capabilities.
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PMID:Primary cultures of neonatal rat liver as an assay system to identify compounds belonging to the tumor promoters class. 389 96

A single exposure to a low concentration (10(-10) mol/l) of tumor promoters [such as 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital and nafenopin] or hormones [such as epidermal growth factor (EGF), glucagon and insulin] or drugs [such as imidazole and indomethacin] stimulated the 24-h flow into DNA synthesis and mitosis of primary neonatal rat hepatocytes incubated in high-calcium (1.8 mmol/l) Eagle's FBS(10% v/v)-MEM. However, only tumor promoters acted as enhancers of hepatocytic DNA synthesis when a low-calcium (0.01 mmol/l) FBS-MEM was used. The activity of tumor promoters was totally suppressed by the simultaneous (or nearly such) addition of low doses (from 25.0 to 0.25 micrograms/ml; activity, from 100 to 0.7 U/ml) of exogenous bovine liver and ox and dog erythrocyte superoxide dismutase (SOD), independent of the calcium concentration of the medium. Even at the minimal dose administered, SOD effectively inhibited the stimulatory actions of TPA concentrations up to 10(-6) mol/l. SOD's blocking effect depended upon its enzymatic activity, as it was prevented by a specific inhibitor of SOD, sodium diethyldithiocarbamate (DDC). By contrast, SOD did not inhibit the growth stimulation elicited by hormones and drugs in hepatocytes maintained in high-calcium FBS-MEM. Moreover, several tumor promoters (namely TPA, phenobarbital, nafenopin, saccharin, teleocidin, benzoyl peroxide, BHT, DDT, lindane, clofibrate and melittin) stimulated DNA synthesis even when the hepatocytes were incubated in the serumless HiWoBa2000 medium, whatever its calcium concentration. In this synthetic medium, tumor promoters' stimulatory activity was again completely inhibited by the simultaneous administration of exogenous SOD. Known antioxidants such as retinoids, vitamin E, selenous acid, and 7,8-benzoflavone, when given simultaneously with TPA, also prevented the stimulation of hepatocytic growth. These results disclose the existence of two quite different mechanisms by which the growth of neonatal rat hepatocytes can be stimulated: (i) the physiological-pharmacological extracellular calcium-dependent SOD-insensitive system mediating the effects of EGF, glucagon, insulin, imidazole, and indomethacin; and (ii) the pathological extracellular calcium-independent SOD- and antioxidant-suppressible mechanism operated by agents belonging to the tumor promoters class and involving, as a critical step, the generation of superoxide anions on the surface of the hepatocyte plasmalemma.
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PMID:Exogenous Cu,Zn-superoxide dismutase suppresses the stimulation of neonatal rat hepatocytes' growth by tumor promoters. 633 36

Epidermal growth factor (EGF) added in a single dose (between 10(-16) and 1.7 X 10(-9)M) to neonatal rat hepatocytes in primary culture with subsequent incubation for 12 and 24 hours in Eagle's MEM fortified with 10% (v/v) FBS stimulated their entry into S and M phases, as shown by (3H)thymidine labeling and autoradiography and by a 4-hour exposure to colchicine (0.1 mM). Growth stimulation by EGF was detectable after 4 hours, peaking between 12 and 16 hours, and thereafter declining in intensity. Rat hepatocytes exposed for 72 hours (between the fourth and the seventh day in vitro) to no serum or to 10% fresh FBS possessed similar growth rates and absolute numbers in the cultures. A 24-hour exposure to 20 to 50% FBS stimulated hepatocytic DNA synthesis and mitotic activity and resulted (except for the 50% FBS treatment) in increased hepatocytes' numbers, which were relatively greater than the concurrent increases in connective tissue cell numbers. In serum-devoid medium EGF (10(-11)M) enhanced hepatocytic mitotic, but not DNA-synthetic activity. To be fully effective EGF required a 10% FBS addition to the medium, then eliciting within 24 hours a marked increase in hepatocytes' number with respect to cultures incubated with 10% serum only. When associated with 20 to 30% FBS, EGF stimulated parenchymal cell growth at rates slightly higher, but not significantly different, than those elicited by the same serum concentrations alone. However, when used in conjunction with 10 to 30% FBS, EGF preferentially increased the number of hepatocytes rather than that of non-parenchymal cells. Moreover, comparative proliferation kinetic studies showed that in the presence of 10% FBS, an equimolar (10(-14)M) mixture of EGF, insulin, and glucagon promoted an early and marked increase in the DNA-synthetic and mitotic activities of hepatocytes, which peaked after 8 hours. Within a 24-hour time lag this growth stimulation was as effective in increasing the final hepatocytes' number as was a 1000-fold higher EGF concentration, and was twice as active as either an equimolar (10(-14)M) mixture of the two pancreatic hormones or EGF by itself at 10(-14)M. These results show that the growth-promoting effect of EGF on primary neonatal rat hepatocytes is modulated by serum factor(s) and can be additively amplified by the simultaneous administration of subphysiological doses of glucagon and insulin.
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PMID:The stimulation by epidermal growth factor (urogastrone) of the growth of neonatal rat hepatocytes in primary tissue culture and its modulation by serum and associated pancreatic hormones. 700 Jul 98

We student basal, glucose- and glucagon-induced insulin secretion in non-insulin diabetes mellitus (NIDDM) patients in relation to body mass index (BMI) and fasting serum glucose (FBS) level. A total of 46 NIDDM patients and 22 control subjects with varying degrees of BMI and FBS were given 100 g of oral glucose and 1 mg of intravenous glucagon on separate days. C-peptide response to glucose, but not basal serum C-peptide and C-peptide response to glucagon, was significantly lower in NIDDM than in controls (P < 0.001). FBS was inversely correlated with C-peptide response to glucose in NIDDM patients (r = -0.67, P < 0.001), but not with basal C-peptide level and C-peptide response to glucagon. On the other hand, BMI was positively correlated with basal serum C-peptide level both in NIDDM (r = 0.60, P < 0.001) and in control subjects (r = 0.74, P < 0.001). In 15 poorly controlled NIDDM patients, the tests were repeated after insulin treatment for 10-14 days. C-peptide response to glucose significantly increase, but not to a level in control subjects, after glycemic control. Basal serum C-peptide level and the C-peptide response to glucagon decreased after glycemic control to significantly lower levels than those in the baseline and those in control subjects. These results suggest that beta cell secretory reserve is reduced in moderate to severe NIDDM patients.
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PMID:Differential effects of ambient blood glucose level and degree of obesity on basal serum C-peptide level and the C-peptide response to glucose and glucagon in non-insulin-dependent diabetes mellitus. 930 37