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

In order to clarify the mechanism of insulin secretion, responses of insulin (IRI) and C-peptide (CPR) in plasma to various stimuli were investigated in normal subjects and patients with diabetes mellitus, liver cirrhosis, chronic nephritis or insulinoma. The response of plasma IRI and CPR to oral glucose load was less marked in the mild and moderate diabetes groups than in the normal controls. Neither IRI nor CPR in the severe diabetes group responded to oral glucose. The patients with liver cirrhosis revealed an exaggerated and delayed response of IRI and CPR, and a lowered CPR/IRI ratio, indicating a remarkable response of IRI to glucose. In contrast, the patients with chronic nephritis showed a prominent rise of CPR alone. In the insulinoma patients, both plasma IRI and CPR increased after glucose load. In the response to glucose, there was approximately 30-min lag time between the peaks of IRI and CPR in the normal controls and the patients with various diseases. Following arginine infusion, plasma IRI and CPR increased in the normal subjects and the patients with moderate diabetes. In the normal subjects, plasma IRI reached a peak at 6 min and 3 min in response to tolbutamide and glucagon, respectively, which elicit an abrupt and sharp rise of insulin from B-cells. However, diabetic patients showed a minimal change in plasma IRI and CPR, whereas there was an exaggerated response of plasma IRI and CPR in insulinoma patients. In analysis of responses of plasma IRI and CPR to tolbutamide or glucagon, there was a lag time longer than 10 min in the normal subjects. The present study confirms the concurrent release of C-peptide from the B-cells in the secretion of insulin. In addition, it was suggested that insulin and C-peptide are mainly handled in the liver and the kidney, respectively. Furthermore, a longer lag time between the peaks of IRI and CPR in response to tolbutamide or glucagon did not necessarily indicate a simultaneous release of insulin and C-peptide from the B-cell, but a delayed release of the latter.
 ...
PMID:Analysis of insulin secretion based on changes in plasma insulin and C-peptide in man. 676 99

The activity of hepatic NADPH cytochrome c reductase, an enzyme important in drug and steroid metabolism, increases rapidly during the perinatal period in rats. However, the regulation of this increase is not well understood. To investigate the role of hormones in the development of NADPH cytochrome c reductase activity, fetal rat livers in organ culture were used in the present study. Explants from 20-day-old fetal rat liver could be maintained for up to 96 h in a serum-free medium with or without added hormones. When the explants were exposed to 50 nM L-T3 for 72 h, they had 74% greater NADPH cytochrome c reductase activity than controls. In contrast, 1 microM hydrocortisone (HC) stimulated reductase activity by only 20%. However, when T3 was added with HC there was a synergistic effect, resulting in a 167% elevation in NADPh cytochrome c reductase activity. The response to T3 plus HC was detectable after 24 h and maximal after 72 h. Control activity rose slightly during the first 48 h in culture and was stable thereafter. Stimulation of reductase activity by T3 was detectable at 0.1 nM, half maximal at 2 nM, and maximal between 10 nM and 100 nM. T4 also stimulated NADPh cytochrome c reductase activity in explants but was only 3-4% as potent as T3. The effect of steroids was specific for glucocorticoids. Neither glucagon nor insulin had any measurable effect on reductase activity. Electron micrographs revealed that hepatic ultrastructure was well preserved for at least 72 h of incubation in the presence or absence of hormones. The data suggest, therefore, that the normal perinatal development of hepatic NADPH cytochrome c reductase activity in rats is regulated at least in part by thyroid hormones acting synergistically with glucocorticoids.
 ...
PMID:Synergistic regulation of fetal rat liver nicotinamide adenine dinucleotide phosphate (reduced form) cytochrome c reductase activity: effects of L-triiodothyronine and hydrocortisone. 680 20

Hormonal and metabolic characteristics of diabetes mellitus in the elderly were investigated in the following groups; elderly DM subdivided into obese DM and non-obese DM, elderly non-DM subdivided into obese and non-DM and non-obese non-DM, adult DM and adult non-DM. Responses of plasma glucose, insulin and glucagon during oral glucose tolerance test (OGTT), arginine tolerance test (ATT) and intravenous glucose tolerance test (IVGTT) were measured individually and the daily urinary C-peptide excretion (U-CRP), fasting plasma levels of free fatty acid (FFA), triglyceride (TD), total cholesterol (TC) and HDL-cholesterol (HDL-C) were also measured. In comparison with adults, insulin responses in IVGTT and ATT in elderly non-DM were low but not in OGTT. It was noteworthy that glucagon response during OGTT in elderly DM was considerably lower than adult DM, probably due to factors other than insulin deficiency. Comparing elderly DM and elderly non-DM, the initial response of insulin in OGTT was found to be low in elderly DM but not in total response. In the comparison between the obese and the non-obese, higher insulin levels in elderly obese DM than in elderly non-obese DM during OGTT, IVGTT and ATT were observed, implying decreased insulin sensitivity. This difference, however, was not apparent between elderly obese non-DM and non-obese non-DM. A good correlation between U-CPR and the response of plasma insulin in OGTT was shown even in the elderly but not between U-CPR and that of plasma insulin in IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Hormonal and metabolic aspects of diabetes mellitus in the elderly]. 831 43

Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to be a risk factor for the development of vascular complications in obese and hyperinsulinemic non-insulin-dependent diabetes (NIDDM) patients. To clarify whether PAI-1 also plays an essential role in the development of such complications in NIDDM patients without obesity or hyperinsulinemia, PAI-1 was analyzed in relation to blood pressure, fasting plasma levels of glucose (FPG), hemoglobin A1C (HbA1c), immunoreactive insulin (F-IRI), C-peptide (CPR), total cholesterol (TC), triglyceride (TGL), and HDL-cholesterol (HDL-C) in 77 NIDDM patients and 10 healthy control subjects. The NIDDM patients were not obese (body mass index [BMI]:<26 kg/m2) or hyperinsulinemic, and BMI in the controls was between 19 and 24 kg/m2. In addition, parameters of insulin secretion reserve, including sigmaIRI, insulinogenic index, and CPR at 5 min after glucagon loading, were evaluated simultaneously. Plasma levels of PAI-1 were higher in the NIDDM group (9.3+/-0.9 ng/ml) than in the controls (4.3+/-0.7 ng/ml;P<0.01). Levels of FPG and HbA1c were also elevated in the NIDDM group (P<0.05 for each), but F-IRI did not differ between the two groups. However, multiple regression analysis revealed no significant correlation in the NIDDM between PAI-1 and F-IRI or the parameters of insulin secretion reserve. Regardless of the presence or absence of vascular complications, PAI-1 did not vary significantly in the NIDDM. These findings suggest that the effects of PAI-1 on the development of diabetic complications in NIDDM patients may not proceed in the same way in those with versus those without obesity or hyperinsulinemia, because no correlation was found between PAI-1 and insulin secretion reserve, while plasma levels of PAI-1 were higher in the NIDDM group than in the controls.
 ...
PMID:Plasminogen activator inhibitor-1 in nonobese subjects with non-insulin-dependent diabetes mellitus. 863 10

In order to evaluate the steady state plasma glucose (SSPG) method by using a new somatostatin derivative, octreotide acetate (Sandostatin) instead of somatostatin that we had used for the insulin sensitivity test, we examined whether octreotide was able to suppress C-peptide (CPR), glucagon (IRG), and GH to a similar degree to that achieved with somatostatin. A total of 52 studies were performed in 45 essential hypertensive subjects and 7 healthy subjects. Octreotide was given subcutaneously in a does of 50 micrograms or 100 micrograms 10 min before the test (sc 50, sc 100 groups) or intravenously infused over 2 h (10 micrograms in bolus followed by a constant infusion, 50, 100, or 150 micrograms/2 h: i.v. 50, i.v. 100, i.v. 150 groups). In all of the groups the plasma immunoreactive insulin (IRI) concentration increased gradually after insulin injection and reached the steady state plasma insulin (SSPI) level between 40 and 60 microU/ml at 60 min through 120 min. Plasma CPR at 120 min was the most suppressed (by 67% of the basal level in i.v. 150 group during the study period), but on the other hand in both the sc 100 and i.v. 100 groups the plasma CPR concentration at 120 min was suppressed by nearly 40%, but not significantly suppressed in either the sc 50 or the i.v. 50 group. Plasma IRG and GH were strongly suppressed after 60 min in all groups during the study period. Plasma glucose had increased significantly at 30 min and reached the steady state at 90 min through 120 min in hypertensive and healthy subjects. The results indicated that the modified SSPG method with continuous intravenous infusion of Octreotide at 150 micrograms/2 h was adequate for the measurement of insulin sensitivity.
 ...
PMID:Modified method using a somatostatin analogue, octreotide acetate (Sandostatin) to assess in vivo insulin sensitivity. 873 63

Serum 7B2 concentrations in control subjects and patients with diabetes mellitus were measured following a 75 g oral glucose load and following intravenous glucagon infusion. In response to oral glucose, serum 7B2 levels increased in the controls (n = 10) and in the diabetic patients (n = 7). The increment of the serum 7B2 level was smaller in the diabetic patients than the controls. During the 75 g oral glucose tolerance test (75g OGTT), serum 7B2 levels were significantly positively correlated with serum C-peptide levels. In contrast, following intravenous glucagon infusion, serum 7B2 levels increased only in diabetic patients treated with oral hypoglycemic agents (n = 20) and did not increase in controls (n = 5): the group having the highest insulin secretion activity in the present study, nor in diet or insulin-treated diabetic patients. No correlation between serum 7B2 levels and serum CPR levels was observed in the intravenous glucagon infusion study. These data suggest that an extra-pancreatic source which produces the observed serum 7B2 increase following oral glucose intake can not be excluded and that 7B2 may not be secreted concomitantly with insulin from the pancreatic beta cell in response to intravenous glucagon injection.
 ...
PMID:Secretory protein 7B2 response to oral glucose loading and intravenous glucagon injection in patients with diabetes mellitus. 901 Nov 9

Skeletal muscle biopsies were performed on 12 healthy sedentary subjects and on 22 non-dyalized chronic renal failure patients (CRF) on a free diet and after overnight fasting. Parathormone, glucagon and insulin were determined at the same time of biopsies. CRF patients showed significantly low ATP and creatine phosphate levels. Regarding enzyme activities, a high hexokinase Vmax was found, while the pyruvate kinase activity was lower than in the control group. For the tricarboxylic acid cycle, citrate synthase, succinate dehydrogenase and malate dehydrogenase activities were higher; total NADH cytochrome c reductase activity was also high, while cytochrome oxidase activity was slightly lower. Both alanine aminotransferase and aspartate aminotransferase activities were considerably high in comparison with the control group. In conclusion, our study revealed a hypermetabolic TCA cycle, but impaired oxidative phosphorylation, which partly explained the reduced ATP concentration. Excessive protein intake and hormonal derangements may play a role in these metabolic changes.
 ...
PMID:Altered muscle energy metabolism in post-absorptive patients with chronic renal failure. 924 94

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity in aged people, insulin sensitivity and secretion was measured by using a two-step euglycemic glucose clamp, a glucagon tolerance test (GTT), an oral glucose tolerance test (OGGT) and urinary CPR excretion in 11 aged patients immobilized in bed for more than 12 weeks. The results were compared with those of nine healthy mobile aged controls. The muscle volume of the immobilized patients decreased by 20-25% compared with that of the controls, and insulin sensitivity decreased 50% in each step. These results mean that the immobilized patients had decreased insulin sensitivity and responsiveness, even when there was muscle atrophy. The glucose and insulin responses in both the GTT and OGTT showed that there was a slight decrease in the initial response of insulin in the immobilized patients and was in the controls compared with adolescent controls. There was no difference in the initial response of insulin between the immobilized patients and the aged controls. The ratio of impaired glucose tolerance in the OGTT was 4/11 of the immobilized patients and 3/9 of the controls. Total insulin secretion was increased and insulin sensitivity and responsiveness was decreased in the immobilized patients. This suggests that the decreased insulin sensitivity was compensated for increased by insulin secretion in the immobilized patients.
 ...
PMID:[Insulin secretin and resistance accompany immobilization of the aged patient]. 945 24

We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than 5 U/ml) and deteriorated secretion of insulin, and clinical course led to the diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were negative. One year prior to the diagnosis, at 78 years of age, she was newly diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose, resulting her glucose levels well-controlled. Four months before admission, a gradual increase of plasma glucose was noticed, while oral hypoglycemic agents were fully administrated. On admission, her glycemic control was revealed as follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%. Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses of subcutaneous insulin (20 units daily) were effective on her diabetes control. She was newly diagnosed with Hashimoto disease that required thyroid hormone replacement 50 micrograms per day after having developed NIDDM. High titer of anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody (81.5 U/ml) were observed. The patient had been medicated for RA with anti-inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to 127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9 recognized to be susceptible to IDDM was detected in the high-elderly onset SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto disease, our case may provide the information to the mechanism of pathogenesis of SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the aged; 75-year-old or more.
 ...
PMID:[Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high elderly]. 977 59

Use of standard ACLS protocols for all patients who are critically poisoned may not result in an optimal outcome. Care of severely poisoned patients can be enhanced by urgent consultation with a medical toxicologist. Alternative approaches required in severely poisoned patients include: o Higher doses than usual. o Drugs that are rarely used to treat cardiac arrest (amrinone, calcium, esmolol, glucagon, insulin, labetalol, phenylephrine, physostigmine, and sodium bicarbonate). o Heroic measures, such as prolonged CPR and use of circulatory assist devices. When resuscitation is unsuccessful, organ donation may still be an option.
 ...
PMID:Part 8: advanced challenges in resuscitation. Section 2: toxicology in ECC. European Resuscitation Council. 1097 5


<< Previous 1 2 3 4 Next >>