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

Substrate utilisation and glucose homoeostasis during exercise is controlled by the effects of precise changes in insulin, glucagon and the catecholamines. The important role these hormones play is clearly seen in people with diabetes, as the normal endocrine response is often lost. In individuals with insulin-dependent diabetes (IDDM), there can be an increased risk of hypoglycaemia during or after exercise or, conversely, there can be a worsening of the diabetic state if insulin deficiency is present. In contrast, it appears that people with non-insulin-dependent diabetes (NIDDM) can generally exercise without fear of a deleterious metabolic response. The exercise response both in healthy subjects and in those with diabetes is dependent on many factors such as age, nutritional status and the duration and intensity of exercise. Since there are so many variables which govern individual response to exercise, an exact exercise prescription for all people with diabetes cannot be made. There are many adjustments to the therapeutic regimen which an individual with IDDM can make in order to avoid hypoglycaemia during or after exercise. In general, a reduction in insulin dosage and the added ingestion and continual availability of carbohydrates are wise precautions. On the other hand, exercise should be postponed if blood glucose is greater than 2500 mg/L and ketones are present in the urine. As more is understood about the regulation of substrate metabolism during exercise, more refined therapeutic strategies can be defined. An understanding of the metabolic response to exercise is critical for generating an effective and safe training programme for all diabetic individuals who wish to be physically active.
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PMID:Physiological bases for the treatment of the physically active individual with diabetes. 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

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

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 determine whether differences in the metabolic response to two common starches could be eliminated by altering the physical form of food, 12 normal and 6 noninsulin-dependent diabetic (NIDDM) subjects were studied after consumption of test loads of whole and blended rice and potato. In normal and NIDDM subjects the lower postprandial glycemia and insulinemia of whole rice was eliminated and became similar to that of whole potato, which was unaffected by blending. The glucagon responses were unchanged and similar in both groups under all study conditions. In both normal and NIDDM subjects the glucose and insulin response to a particular starch is not a stable feature dependent on the unique characteristics of the starch molecule but is affected by food processing and the form in which it is presented to the gastrointestinal tract.
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PMID:Postprandial metabolic responses to the influence of food form. 304 97

Glyburide, a second-generation sulfonylurea, is used in the treatment of NIDDM because of its hypoglycemic action. However, the site and mechanism of action of this sulfonylurea remain unclear. We examined the ability of glyburide to enhance insulin's inhibitory effect on glucagon-stimulated hepatic glucose production. The livers of fed male rats were perfused with a Krebs-Henseleit buffer containing washed human red blood cells. After a 60-min control period during which the liver was exposed to both insulin and glucagon (10 microU/ml and 11 pg/ml, respectively), the glucagon concentration was increased to 88 pg/ml in the presence of 0, 10, 40, and 240 microU/ml of insulin. Hepatic glucose output and phosphorylase a activity were monitored during the control and elevated-glucagon periods. The glyburide-infused group received glyburide (1.6 microgram/ml) during both the control and elevated-glucagon periods. As expected, high levels of insulin suppressed glucagon-stimulated glucose production and phosphorylase activation. Insulin at a concentration of 10 microU/ml was unable to suppress glucagon's stimulation of glucose production or its activation of phosphorylase. However, in the presence of glyburide it was able to decrease stimulated hepatic glucose production and phosphorylase activation by 40 and 50% respectively. In the absence of insulin, glyburide was unable to suppress glucagon's glycogenolytic action, suggesting that the drug potentiates insulin's action on the liver rather than exerting an inhibitory effect directly. Insulin at a concentration of 240 microU/ml completely suppressed glucagon action, and glyburide had no additional effect. Therefore, glyburide is able to enhance the sensitivity of the perfused rat liver to insulin without altering maximal insulin responsiveness.
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PMID:Glyburide sensitizes perfused rat liver to insulin-induced suppression of glucose output. 310 99

The endogenous insulin secretion capacity of 171 insulin-treated middle-aged persons with diabetes (81 men, 90 women) of the Kuopio University Central Hospital district (population 250,000), East Finland, was measured by the C-peptide response to glucagon. The prevalence of insulin deficiency among initially non-insulin-dependent diabetic (NIDDM) individuals was calculated on the basis of those who were initially treated with diet or oral drugs and 3 yr or more after diagnosis had been treated with insulin and were insulin deficient in this study. The prevalence of complete insulin deficiency (postglucagon C-peptide undetectable) was among initially NIDDM individuals of the same region, 0.7% in men and 1.2% in women. Using the postglucagon C-peptide level of 0.20 nmol/L as a cut-off point, the prevalence of insulin deficiency was 2.0% in men and 1.9% in women and, on the basis of C-peptide level of 0.60 nmol/L, the prevalence of insulin deficiency was 3.5% in men and 2.7% in women. Our data suggest that the deterioration of insulin secretion capacity in NIDDM to the level that leads to insulin dependency occurs less often than has been previously suggested.
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PMID:Prevalence of insulin deficiency among initially non-insulin-dependent middle-aged diabetic individuals. 352 53


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