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)

The application of immunofluorescence technique with anti-insulin, anti-glucagon, anti-somatostatin, and anti-pancreatic polypeptide (PP) antisera to sections of precisely sampled regions of the human pancreas allowed the quantitative evaluation of the total content of these four endocrine cell populations in 13 nondiabetics, in 2 insulin-dependent diabetics (IDDM), and in 2 non-insulin-dependent diabetic subjects (NIDDM) of various age and sex. In nondiabetic subjects, PP-cells appear sex-related. Male individuals have a significantly greater volume of PP-cells than female. In diabetic subjects, the only marked difference as compared with nondiabetics is the reduction of insulin cell volume in IDDM. Other small differences between individual endocrine cell volumes are detectable in both IDDM and NIDDM as compared with nondiabetics, but their significance is at present unclear. The qualitative changes of islet structure accompanying insulin cell reduction in IDDM were not considered in the present study.
 ...
PMID:Quantitation of endocrine cell content in the pancreas of nondiabetic and diabetic humans. 613 Oct 2

To assess the relationship between beta-cell function and the level and duration of hyperglycemia during generalized beta-cell impairment, we studied the effects of acute and prolonged infusion of somatostatin in seven normal men. Twenty minutes after beginning an acute infusion of somatostatin (200 microgram/h) plus glucagon replacement (0.75 ng/kg/min), plasma glucose (PG) remained unchanged, but plasma insulin (IRI) and acute insulin response to isoproterenol had fallen markedly. Seventy minutes after beginning somatostatin-plus-glucagon, a rise in PG was associated with an increase in the acute insulin response to isoproterenol, though not to the control level. In a separate study, after 46 h of the somatostatin-plus-glucagon infusion, at a glucose level similar to the 70-min level, plasma insulin had returned nearly to the control level and the acute insulin response to isoproterenol had returned completely to the control level. Such increases inb basal and stimulated insulin secretion most likely represent a time-dependent adaptation by the beta-cells to the persistent hyperglycemia. First- and second-phase insulin responses to intravenous glucose were markedly inhibited after 46 h of somatostatin-plus-glucagon. In summary, a 46-h infusion of somatostatin with glucagon replacement in humans leads to hyperglycemia, a slightly diminished basal insulin level, markedly decreased insulin responses to glucose, and an insulin response to isoproterenol maintained at a normal level by acute and probably chronic adaptation to the hyperglycemia. We speculate that beta-cell adaptation to hyperglycemia may explain the similar abnormalities of islet function observed in patients with NIDDM.
 ...
PMID:Hyperglycemia and beta-cell adaptation during prolonged somatostatin infusion with glucagon replacement in man. 613 30

The AA. studied the glycometabolic activity of prazosin, a hypotensive drug with an adrenergic blocking activity of alpha-1-selective type. Twenty-two moderately hypertensive subjects were studied. Their ages ranged from 37 to 57 years; 10 of the patients had non-insulin dependent diabetes mellitus. After overnight fasting every patient underwent an oral glucose test (g 100) at 09:00. Blood samples were withdrawn at 0, 30, 60, 90 and 120 minutes. Each patient was then given in randomized and double-blind fashion placebo or prazosin (4 mg, 2 pills of Minipress Pfizer per day) for the following 7 days; then another glucose load was administered. Glucose (enzymatic method), insulin and glucagon (RIA method) were measured in each blood sample. In non diabetic subjects glucose levels (60, 90, 120 min and total area) after oral glucose and prazosin were statistically higher (p less than 0.05, p less than 0.01, p less than 0.05) than after glucose only. No significant difference between the two curves was observed in the diabetic group. IRI levels in normal subjects were statistically higher after 120 min and in the total area, while no evident changes were noted in the diabetic group. The glucagon curve seen after oral glucose was not modified by prazosin in either group.
 ...
PMID:Effect of alpha-1-blockade by prazosin on blood sugar, insulin and glucagon levels in normals and non-insulin dependent diabetics. 613

The present study was designed to determine the effect of naloxone, a specific opiate receptor antagonist, on postprandial levels of insulin, glucagon, pancreatic polypeptide (PP), somatostatin-like immunoreactivity (SLI) and gastrin in response to carbohydrate and fat-rich test meals in a group of 6 healthy volunteers. The addition of naloxone to a meal consisting of 50 g sucrose dissolved in 200 ml water augmented the rise of plasma insulin levels significantly during the first 30 min after its ingestion and reduced the rise in plasma insulin and pancreatic polypeptide and elevated glucagon levels during the last 30 min of the experimental period. When sucrose was dissolved in 200 ml cream the addition of naloxone augmented the postprandial rise of insulin levels between 15 and 60 min after ingestion of the meal and elicited an increase of plasma SLI and PP levels throughout the entire experimental period which indicates that post-prandial levels of insulin, glucagon, PP and SLI are modulated via endogenous opiate receptors during the ingestion of carbohydrate and fat test meals and that this effect depends on the composition of the ingested nutrients. These data raise the possibility that endogenous opiates participate in the regulation of postprandial insulin, glucagon, somatostatin and pancreatic polypeptide release not only in certain disease states as demonstrated recently for insulin secretion in type II diabetes mellitus but endogenous opiates may also be of importance under physiological conditions.
 ...
PMID:Effect of naloxone on pancreatic and gastric endocrine function in response to carbohydrate and fat-rich test meals. 614 5

This study was undertaken to investigate the effect of experimental type 2 diabetes in the rat on the insulin and glucagon receptors and on the early steps of glucagon action. The binding of insulin and glucagon and the glucagon-stimulated cyclic AMP accumulation in the presence of a phosphodiesterase inhibitor (IBMX, 0.1 mmoles/l) were studied in liver cells isolated from 7-9-month-old rats with chronic type 2 diabetes and from control rats. No significant change was observed in [125I] insulin binding and [125I]glucagon binding of diabetic liver cells as compared to controls. Scatchard analysis of the competition experiments indicated that affinity and number of insulin and glucagon receptors were not significantly changed in the liver cells of diabetic rats. The basal cyclic AMP level was significantly lower in the diabetic hepatocytes (2.3 +/- 0.9 pmoles/10(6) cells) than in the controls (4.0 +/- 0.6 pmoles/10(6) cells). Cyclic AMP response to physiological concentrations of glucagon (0.1-1 nmoles/l) was about 2 times lower in the diabetic hepatocytes than in the controls. Furthermore, the basal liver membrane adenylate cyclase activity and the fluoride-activatable adenylate cyclase activity were about 2 times lower in the diabetics as compared to control rats, while the liver cyclic AMP and cyclic GMP phosphodiesterase activities were unchanged. The ability of glucagon to stimulate liver membrane adenylate cyclase over a 10(-12)-10(-6) M concentration range was decreased in diabetic rats. Taken together, these data are consistent with the thesis that the impairment of the liver cyclic AMP response to glucagon in rats with type 2 diabetes is caused by a decrease in the amount of adenylate cyclase in the liver plasma membranes.
 ...
PMID:Decreased glucagon-stimulated cyclic AMP production by isolated liver cells of rats with type 2 diabetes. 631 52

Prostaglandins of the E series are implicated as regulators of glucose homeostasis because of their effects on glucose production and secretion of insulin and glucagon. PGE is postulated to play a role in the pathophysiology of insulin secretion in adult-onset (Type II) diabetes mellitus. Evidence supporting this hypothesis includes the demonstration that PGE inhibits glucose-induced acute insulin responses in normal humans. Moreover, drugs that inhibit synthesis of PGE improve abnormal insulin secretion in human subjects with Type II diabetes mellitus.
 ...
PMID:Prostaglandins, glucose homeostasis, and diabetes mellitus. 634 49

To ascertain whether the dawn phenomenon occurs in nondiabetic individuals and, if so, whether it is due to an increase in glucose production or a decrease in glucose utilization, we determined plasma concentrations of glucose, insulin, C-peptide, and counterregulatory hormones, as well as rates of glucose production, glucose utilization, and insulin secretion at one-half-hourly intervals between 1:00 and 9:00 a.m. in eight normal volunteers. After 5:30 a.m., plasma glucose, insulin, and C-peptide concentrations all increased significantly; rates of glucose production, glucose utilization, and insulin secretion also increased (all P less than 0.05). Plasma cortisol, epinephrine, and norepinephrine increased significantly from nocturnal nadirs between 4:00 and 6:30 a.m. Plasma growth hormone, which had increased episodically between 1:00 and 4:30 a.m., decreased thereafter nearly 50% (P less than 0.05). Plasma glucagon did not change significantly throughout the period of observation. These results indicate that a dawn-like phenomenon, initiated by an increase in glucose production, occurs in nondiabetic individuals. Thus, early morning increases in plasma glucose concentrations and insulin requirements observed in IDDM and NIDDM may be an exaggeration of a physiologic circadian variation in hepatic insulin sensitivity induced by antecedent changes in catecholamine and/or growth hormone secretion.
 ...
PMID:Demonstration of a dawn phenomenon in normal human volunteers. 638 30

A description is given of the electron microscopic-morphometric findings obtained for the islets of Langerhans of the pancreas and for the glucagon-producing A cells of one patient suffering from longstanding insulin-dependent diabetes mellitus (IDDM, type I diabetes), two patients with longstanding insulin-independent diabetes mellitus (NIDDM, type II diabetes), and one non-diabetic. A morphometric determination of the volume densities of the vascular connective tissue and the various endocrine cells per islet tissue and organelles/ultrastructures per A cell was made, and the diameters of the A-granules were measured. So far, no such studies have been made for human diabetes mellitus, and only a few are available for humans with sound metabolism. In general, the qualitative and, particularly, the quantitative electron microscopic results found for the IDDM patient show greater and clearer deviation from the control with normal metabolism than the findings obtained for the NIDDM patients. As regards the cellular composition of the pancreatic islets and changes caused by diabetes mellitus, the morphometric values obtained from electron micrographs are in essential agreement with comparable findings reported in the literature for light microscopic-histochemical and -immunohistochemical morphometry. The patient with insulin-dependent diabetes has a higher proportion of vascular connective tissue in the pancreatic islets than the non-diabetic. This increase is both relative and absolute and is primarily connected with the loss of B cells in this type of diabetes. In the IDDM patient, A cells were found in the islets but also scattered as single cells in the exocrine tissue and in the walls of pancreatic ductules. The ultrastructural composition of the A cells varies within wide limits even in persons with sound metabolism. Diabetes mellitus does not cause major qualitative alterations in the A cells. The A cells of the IDDM patient contained a remarkable number of nuclei and rarely showed A-granule crinophagia. The casuistic electron microscopic findings, most of which have been obtained for the first time, are discussed. Nothing can be said at this stage about the general applicability of the findings. The morphometric results obtained for the A cells can be interpreted as indicating increased metabolism with heightened glucagon synthesis and secretion in the case of the insulin-dependent diabetic and, to a lesser extent, in the NIDDM patients. This interpretation would support the assumption of a normally existing mutual local paracrine regulation of the A and B cells which stems from close topographical relations (contact, gap junctions).
 ...
PMID:[Electron microscopic findings in A-cells of the islands of Langerhans in diabetes mellitus]. 639 63

Dynamics of insulin and glucagon secretion were investigated by using a new model of spontaneous diabetes rats produced by the repetition of selective breeding in our laboratories. The perfusion experiments of the pancreas showed that the early phase of insulin secretion to continuous stimulation with glucose was specifically impaired, although the response of the early phase to arginine was preserved. The glucose-induced insulin secretion in the nineth generation (F8) which had a more remarkably impaired glucose tolerance was more reduced than in the sixth generation (F5). No significant difference of glucagon secretion in response to arginine or norepinephrine was noted between the diabetes rats and control ones. The present data indicate that the defective insulin secretion is a primary derangement in a diabetic state of the spontaneous diabetes rat. This defect in the early phase of glucose-induced insulin secretion suggests the specific impairment of the recognition of glucose by the pancreatic beta-cells. The spontaneous diabetes rats are very useful as a model of disease for investigating pathophysiology of non-insulin dependent diabetes mellitus.
 ...
PMID:Impaired insulin secretion in the spontaneous diabetes rats. 675 Aug 45

To ascertain whether the ability of glucose to influence the pancreatic islets response to a nonglucose stimulus is normal in type II diabetics, we have evaluated the modulating effect (Md) of the plasma glucose level (PG) on the acute insulin response (IRI) and glucagon response (IRG) to intravenous arginine in noninsulin-dependent diabetics (NIDDM) and nondiabetics (ND). MdIRI or MdIRG is the change in the hormonal response to arginine resulting from changes in plasma glucose level divided by the change in plasma glucose. Md has been determined over two ranges of PG: between normal fasting PG (level I) and mild hyperglycemia (approximately 160 mg/dl, level II) and between mild hyperglycemia and marked hyperglycemia (approximately 350 mg/dl, level III). Increases in PG augmented the IRI response in both groups, but the degree of augmentation was impaired in the NIDDM group. MDIRI for ND and NIDDM between levels I and II were 20 +/- 3 and 1.9 +/- 0.6, respectively, and between levels II and III were 23 +/- 5 and 2.3 +/- 0.5, respectively (P less than 0.01). MdIRI correlated with fasting PG in ND and NIDDM. Changes in PG resulted in equivalent changes in the IRG response to arginine in both groups. MdIRG for level I to II was -6.2 +/- 1.0 and -6.0 +/- 1.2, and for level II and III was -0.9 +/- 0.4 and -1.2 +/- 0.5 in ND and NIDDM, respectively. The impairment of MDIRI and its relationship to fasting PG in NIDDM support the hypothesis that fasting hyperglycemia may be, in part, a compensatory mechanism for maintaining beta-cell response to nonglucose stimuli, thereby maintaining basal insulin levels. MdIRG was normal in NIDDM when evaluated at comparable glucose levels in the ND and NIDDM groups.
 ...
PMID:Glucose modulation of insulin and glucagon secretion in nondiabetic and diabetic man. 675 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>