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)

The effect of nifedipine 40 mg.day-1 for 3 months on glucose tolerance, insulin and C-peptide secretion after an oral glucose tolerance test (OGTT), intra-venous glucose tolerance test (IVGTT) and glucagon stimulatory test, has been studied in 8 moderately hypertensive women suffering from non-insulin dependent diabetes mellitus (NIDDM). No significant variation in glucose metabolism was noted after nifedipine treatment, except for a slight improvement in insulin secretion after OGTT at the end of the study. There was an increase in cholesterol as a collateral effect.
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PMID:Insulin secretion and glucose tolerance in non-insulin dependent diabetic patients after chronic nifedipine treatment. 266 24

Authors studied plasma C-peptide in basal period and after stimulation with one mg of glucagon intravenous in 73 patients with NIDDM. The results have confirmed initial clinical diagnosis of NIDDM. Significative correlations were obtained between basal C-peptide and C-peptide response to glucagon (r = 0.861; p less than 0.01); delta C-peptide (difference between C-peptide basal and after response to glucagon) (r = 0.361; p less than 0.01); body mass index (r = 0.423; p less than 0.01). The significant correlations between basal C-peptide, C-peptide response to glucagon and delta C-peptide show that basal C-peptide measurement is a sufficient test for beta-cell secretory capacity, even though do not give indicative signs for therapy choice of NIDDM for its multifactorial pathogenesis.
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PMID:[Evaluation of beta cell function in non-insulin-dependent diabetes mellitus (NIDDM) and its correlations with clinico-metabolic parameters]. 266 24

Fasting concentration of the C peptide in serum was estimated in 150 patients with type 2 diabetes treated with insulin because of the late, true ineffectiveness of the sulphonylurea derivatives. In 36 patients selected out of the total group at random the secretion of that peptide was measured after i.v. injection of 1 mg of glucagon. Only 9 patients showed trace amounts of that peptide at morning fast (Group A--0.17 +/- 0.08 nmol/l), in 69 the secretion was normal (Sub-Group B1--0.80 +/- 0.25 nmol/l), in 48 moderately elevated (Sub-Group B2--1.67 +/- 0.10 nmol/l) and in 24 markedly elevated (Sub-Group B3--4.54 +/- 2.57 nmol/l). The increments of the peptide C concentration after glucagon stimulation were parallel to its fasting concentration, which indicated a proper reactivity of the pancreatic beta-cells in patients with normal or increased basal secretion. The patients with only trace secretion of the peptide C differed from the other by their small, normal body mass and by a longer duration of insulin treatment. Very similar insulin needs must be stressed in the patients of the Groups A and B as well as within the Sub-Groups B. In patients with hyperactivity of the beta-cells (Sub-Group B2 and B3) no differences were found, as compared with the other patients, in the prevalence of chronic diabetes complications of the micro- or macroangiopathy type, also prevalence of hypertension was equal. The results presented show that in the most patients with type 2 diabetes, with the late, true ineffectiveness of the sulphonylurea derivatives the secretory function of the pancreatic islets beta-cells remains normal or is even increased.
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PMID:[Functional capacity of pancreatic B cells in patients with diabetes mellitus type 2 with late true ineffectiveness of sulfonylurea derivatives]. 269 67

The neonatal streptozocin (STZ) rat model of NIDDM has been previously found to have a markedly reduced insulin response to an acute increase in glucose concentration. We studied the effect of an acute reduction in glucose concentration on insulin and glucagon secretion in this model and contrasted the results with the effects of epinephrine and somatostatin using the in vitro isolated, perfused pancreas. The reduction in perfusate glucose concentration from 11.1 to 2.8 mM caused a rapid suppression of insulin release in the control rats, but had no inhibitory effect in the STZ group. Epinephrine (55 nM) and somatostatin (110 nM) caused similar decreases in insulin secretion in both groups. The glucose reduction also caused an increase in glucagon release in the controls, but had no effect in the STZ rats. Epinephrine, however, stimulated glucagon secretion in both groups in a similar fashion, and inhibition by somatostatin was also comparable. The baseline insulin and glucagon concentrations were enhanced in a separate series of experiments by the addition of arginine (5 mM) to the perfusate, and while the insulin and glucagon responses to the glucose reduction remained lost, appropriate inhibition of insulin secretion was demonstrated in the STZ rats with epinephrine. These data indicate that A- and B-cells in this rat model of NIDDM are selectively unresponsive to both increases and decreases in glucose concentration, while the responsiveness to nonglucose agents remains intact.
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PMID:Unresponsiveness to glucose in a streptozocin model of diabetes. Inappropriate insulin and glucagon responses to a reduction of glucose concentration. 286 Nov 28

The prevention or correction of hypoglycemia is the result of both dissipation of insulin and activation of counterregulatory systems. In the models studied to date, glucagon and epinephrine have been shown to be the key counterregulatory factors; the potential roles of other hormones, neural factors, or substrate mechanisms in other models and during more gradual recovery from hypoglycemia remain to be defined. Deficient glucagon responses to decrements in plasma glucose, which are common in patients with IDDM and occur in some patients with NIDDM, result in altered counterregulation. But counterregulation is generally adequate, because epinephrine compensates for it. Defective glucose counterregulation due to combined deficiencies of glucagon and epinephrine secretory responses occurs in many patients, typically those with longstanding diabetes, and must be added to the list of factors known to increase the risk of hypoglycemia, at least during intensive therapy. From the material reviewed, it should be apparent that much has been learned about glucose counterregulation. It should be equally clear that much remains to be learned. Among the many possibilities, we consider four worthy of emphasis. First of all, we need to examine the physiology and pathophysiology of glucose counterregulation in additional models (e.g., during exercise) and over longer periods. Secondly, we need to determine whether central nervous system adaptation to antecedent glycemia occurs and, if so, identify its mechanisms. Thirdly, we need to develop better methods of insulin delivery or learn to correct or compensate for defective counterregulatory systems, if we are to achieve euglycemia safely in diabetic patients with defective glucose counterregulation. Finally, we need to know whether effective control of diabetes mellitus prevents development of defective glucose counterregulation.
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PMID:Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus. 286 65

The use of hospital services was studied in 228 patients with known diabetes (KD) (52 insulin treated. 101 diet plus oral hypoglycaemic agents (OHAs), 66 diet treated and 9 without treatment) and 87 subjects with fasting hyperglycaemia (FH) found by screening of a well-defined population aged 60-74 years. Ninety per cent were NIDDM as evaluated by a high C-peptide response on glucagon stimulation. Information about all admissions during the year before ascertainment was obtained from the complete regional computerized hospital registration system. The overall average admission rate per year for KD males was 0.47 and for females 0.50. The average number of bed-days occupied per person-year was 6.8 for KD males and 8.2 for females. These rates are 2-3 times higher than those of the general population. Insulin treated NIDDM patients had a rate of 23.9, whereas IDDM patients had a rate of 15.2 bed-days per person-year. The corresponding figures for patients treated with OHAs were 3.5 and for patients treated with diet 4.6. FH had overall bed-day occupancy rates of 0.50 and 1.09 for males and females, respectively, which was less than half of that expected from the general population. IF discharge diagnosis (principal and/or subsidiary) had been used for identification of hospitalized patients with diabetes the bed-days used by KD patients would have been underestimated by 15.3%, most pronounced for diabetics treated with OHAs (21.1%) or diet (21.6%).
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PMID:Use of hospital services by elderly diabetics: the Frederica study of diabetic and fasting hyperglycaemic patients aged 60-74 years. 295 43

Hormonal and glycemic changes in 22 rhesus monkeys were characterized during the first days after treatment with streptozotocin (STZ) (45 to 55 mg/kg, administered intravenously [IV]). Almost half (10/22) of the monkeys developed insulin-dependent diabetes mellitus (STZ-IDDM) within five days following injection. Four of the remaining monkeys did not become insulin dependent for at least 6 months after STZ treatment, during which time they were considered non-insulin-dependent, and eight monkeys never required exogenous insulin. In the STZ-IDDM group, plasma immunoreactive c-peptide (IRC-P) levels fell by three hours after STZ from a mean +/- SEM of 252 +/- 82 to 101 +/- 45 pg/mL, as glucose and immunoreactive glucagon (IRG) levels increased from 65 +/- 3 and 120 +/- 37, respectively, to 336 +/- 43 mg/dL and 234 +/- 52 pg/mL, respectively. Between six and 30 hours after treatment, IRC-P increased to a peak of 1,561 +/- 360 pg/mL before falling permanently to less than 60 pg/mL by 66 hours. During this period, glucose and IRG responded in a reciprocal fashion by falling and then increasing to levels above 300 mg/dL and 300 pg/mL, respectively, by 66 hours. In the non-insulin-dependent diabetes mellitus (STZ-NIDDM) group, no clear reciprocal relationship between IRC-P and glucose and IRG was obtained. In nine additional monkeys subjected to total pancreatectomy (Px), IRC-P and IRG levels fell immediately and permanently by greater than 90% and 75%, respectively. Levels of immunoreactive somatostatin increased steadily over the initial 96 hours following STZ, but did so both STZ-IDDM and Px monkey groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical changes in rhesus monkey during the first days after streptozotocin administration are indicative of selective beta cell destruction. 296 84

Glucagon may play a role in the metabolic derangements of overt Type 2 (non-insulin-dependent) diabetes mellitus. We therefore have evaluated the early steps in glucagon action by investigating the hormone-sensitive adenylyl cyclase system in liver membranes from seven Type 2 diabetic patients with fasting hyperglycaemia and two-fold elevations in plasma glucagon. The comparison was made with seven control subjects matched for age, sex and body weight. Glucagon receptor binding was almost identical in the two groups. There were, however, marked alterations in the adenylyl cyclase activity in membranes from the diabetic patients. This activity was reduced by 35-50% when compared to control activity. Basal cyclase activity, as well as the activity after stimulation with glucagon or with agents (i.e., sodium fluoride and forskolin) that act beyond the glucagon receptor, was significantly decreased (p less than 0.05, p less than 0.001 respectively). In conclusion, uncontrolled Type 2 diabetes in associated with an over-all loss of responsiveness of the hormone-sensitive adenylyl cyclase in human liver, which apparently results from post-receptor alterations. This change may provide a mechanism for reducing the effect of hyperglycagonaemia in Type 2 diabetes mellitus.
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PMID:Altered action of glucagon on human liver in type 2 (non-insulin-dependent) diabetes mellitus. 303 42

Although there are abnormalities in the function of pancreatic alpha, delta, and PP cells in NIDDM, only in the case of the glucagon-secreting alpha cells is there sufficient evidence to indicate that these abnormalities may be metabolically important. But the cause of abnormal glucagon secretion remains to be established. Studies of delta-cell secretion have been hampered by the inability to determine the source of circulating somatostatin-like immunoreactivity and the failure to distinguish between the potential molecular species being measured. Pancreatic polypeptide remains a hormone in search of a metabolic function; the main use of its measurement may be in the study of parasympathetic nervous system function in NIDDM.
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PMID:Non-beta-cell islet abnormalities in noninsulin-dependent diabetes mellitus. 304 41

To test the hypothesis that short-term insulin therapy may induce long-lasting metabolic improvements in patients with type 2 diabetes resistant to oral therapy, 19 patients were studied before and four weeks after insulin therapy, and again four weeks after resumption of oral medication. The mechanisms associated with changes of glycemic control after discontinuation of insulin therapy were also evaluated. During insulin therapy, blood glucose levels (228 +/- 13 versus 123 +/- 18 mg/dl, p less than 0.001) and the basal glucose production rate (p less than 0.001) decreased, and the insulin secretory response to glucagon at a standardized glucose level, insulin action in vivo, and insulin binding and action in vitro in fat cells improved significantly. During the post-insulin oral therapy, blood glucose levels increased (194 +/- 11 mg/dl, p less than 0.001) but remained below pre-insulin treatment values (p less than 0.01). The mean daily glucose concentration after post-insulin oral therapy correlated with the initial pre-insulin therapy glucose concentration (r = 0.83, p less than 0.001). The improved rate of in vivo glucose disposal and the enhanced insulin secretory response persisted during oral therapy whereas the basal glucose production rate returned to its pre-insulin therapy value. It is concluded that patients with type 2 diabetes in whom oral therapy fails show favorable responses to insulin therapy. After discontinuation of insulin therapy, blood glucose concentrations tend to return to their individual initial values. Therefore, most of these patients require long-term insulin therapy. The mechanism behind the change of glycemic control after cessation of insulin therapy seems to be an increase in the basal glucose production rate rather than deterioration of extrahepatic insulin action or the insulin secretory response.
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PMID:Clinical benefits and mechanisms of a sustained response to intermittent insulin therapy in type 2 diabetic patients with secondary drug failure. 304 67


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