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)

Intrajejunal infusion of hypertonic glucose and hypertonic saline inhibits pentagastrin-stimulated gastric acid secretion in man. This effect is generally ascribed to the hyperosmolality of the solutions. Five volunteers were given 50 g glucose in osmolar concentrations of 2700 mosmol/l and 900 mosmol/l, and five were given 25 g glucose in osmolar concentrations of 2700 mosmol/l and 300 mosmol/l. Control studies with intrajejunal infusion of physiologic saline were performed in all subjects. Median inhibition of gastric acid secretion was 91% after 50 g glucose and 47% after 25 g glucose and was unrelated to the osmolar concentration. These findings suggest that the acid-inhibitory effect of intrajejunally administered glucose is related to the glucose load and not to the osmolar concentration. Plasma responses of intact neurotensin, immunoreactivity, NH2-terminal neurotensin immunoreactivity, enteroglucagon, and gastric inhibitory polypeptide were all related to the amount of glucose given. Glucagon and somatostatin, both of which are potent inhibitors of gastric secretion, were not released by intrajejunally administered glucose.
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PMID:Inhibition of gastric acid secretion by jejunal glucose and its relation to osmolality and glucose load. 196 87

Ketoacidosis, severe hyperosmolality due to hyperglycemia, and severe hypoglycemia are all life-threatening emergencies that often occur in the absence of any history of diabetes mellitus. The key to management of diabetic ketoacidosis is understanding that treatment is aimed more at the breakdown and metabolism of triglycerides in adipose tissue than at hyperglycemia per se. The diabetic hyperosmolar state is most easily treated with aggressive fluid management, with the caveat that too-rapid administration of hypotonic fluids may increase the already significant mortality from this condition. Life-threatening hypoglycemia most commonly occurs with administration of oral hypoglycemic drugs or insulin, although other drugs and any malnourished state may also be precipitating factors. Acute administration of glucagon or dextrose alleviates life-threatening hypoglycemia. Success in managing these diabetic emergencies depends on rapidity of recognition and institution of direct treatment measures.
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PMID:'Diabetic' emergencies. They happen with or without diabetes. 211 37

To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on basal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg-1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg-1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation's fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3-O-methylglucose and uptake of 2-deoxyglucose at 400 vs. 300 mosm kg-1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P less than 0.025) by increased osmolality for 2-deoxyglucose (16%) than for 3-O-methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.8% when the osmolality was raised to 400 mosm kg-1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.
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PMID:Effect of hyperosmolality on basal and hormone-stimulated hepatic glucose metabolism in vitro. 249 70

Hyperglycemia-inducing hyperosmolality has recently been proven beneficial in the maintenance of blood volume and extracellular fluid volume during early hemorrhagic hypotension. Fed animals benefitted from better plasma refill compared with starved ones when subjected to equal blood loss. Using lightly sedated fed and 24-30 h starved rats, hormones with relevance to glucose homeostasis were studied during 90 min of hemorrhagic hypotension of 70 mmHg (1 mmHg = 133.32 Pa). Marked differences in the overall hormonal developments were found between the two groups. In fed rats, insulin and glucagon responses were initially attenuated, while somatostatin increased to an early peak level at 30 min, returning to basal at 90 min. In starved rats, somatostatin increased gradually during the 90 min. Adrenaline release was massive in both groups. Corticosterone showed no increase from basal levels in the fed group during hemorrhage, while starved rats increased their basal level fourfold already at 30 min. These data are presented as evidence that changing nutritional status alters hormonal response to hypovolemic stress.
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PMID:Nutritional status and endocrine response to hemorrhage. 287 24

To determine whether glucagon plays a significant role in the restitution of blood volume after hemorrhage, pentobarbital-anesthetized dogs were treated with somatostatin (SRIF). The administration of SRIF (14 micrograms/kg.h) prevented the increase in osmolality and the complete restitution of plasma protein and blood volume that normally occur after 10% hemorrhage. The intraportal addition of glucagon (20 ng/kg.min) during the initial 4 h after hemorrhage reversed the SRIF-induced block in hyperosmolality and was followed by complete restitution of plasma protein and blood volume. These data suggest that increases in glucagon may be a part of the multi-hormonal response to hemorrhage, and this may be a part of a reflex that mediates the homeostasis of blood volume.
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PMID:Restitution of blood volume after hemorrhage: inhibition by somatostatin. 612 60

Gastric stress ulcers were produced by restraint in nonsecretory rats, and the response of the ulcer index to intraduodenal hydrochloric acid (HCl) or sodium chloride (NaCl) was studied in a three-step dose-response trial. Both substances lowered the ulcer index dose-dependently (Km HCl 0.038 +/- Km NaCl 0.089 +/- 0.009 mM/kg/h, respectively) reaching a nadir in rats receiving HCl. The improvement in ulcerations was associated with elevated plasma secretin, glucose, and lowered gastrin in this protocol. In both experimental procedures plasma vasoactive intestinal peptide (VIP) was higher with the low and intermediate doses as compared with the high dose when a slight venous hyperosmolality was present. Glucagon and insulin remained essentially stable. It is concluded that stress ulcers of the restraint type may be prevented by intraduodenal HCl, suggesting that the interplay of gastrointestinal hormones is deranged by stress and partly restored by acid instillation.
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PMID:Gastric stress ulcers and gastrointestinal hormones - response to hydrochloric acid and sodium chloride infused intraduodenally. Preliminary report. 721 4

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the two most serious metabolic complications of diabetes mellitus (DM). These disorders can occur in both type 1 and type 2 DM. DKA is characterized by hyperglycemia, ketone body formation and metabolic acidosis. Precipitating causes are usually infection or insulin omission. Over the past 20 years, there has been no reduction in the DKA mortality rates, which remain between 3.4% and 4.6%. HHS is manifested by marked elevation of blood glucose, hyperosmolality and little or no ketosis. Precipitating causes of HHS are infection, undiagnosed diabetes and substance abuse. The mortality rates of the HHS remain high at approximately 15%. Basic common pathophysiological mechanisms in both conditions, which differ only in the magnitude of dehydration and degree of ketoacidosis, are the reduction in the effective insulin action combined with increased counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). While in DKA the lack of insulin combined with increased catecholamines results in accelerated lipolysis and thus production of excess fatty acids, leading to beta-oxidation and ketogenesis, in HHS residual beta-cell function is adequate to prevent lipolysis but not hyperglycemia. The prognosis of both conditions is substantially worsened in patients > 65 years of age and in the presence of coma and hypotension. Mainstays of therapy are intravenous insulin and fluid replacement as well as the concomitant treatment of the precipitating factors. Improved patient education and implementation of measures such as home glucose and ketone monitoring might decrease the number of hospital admissions due to DKA and HHS, which are, in their majority, preventable).
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PMID:Diabetic ketoacidosis and hyperosmolar hyperglycemic state. 1680 31

According to WHO data more than 180 million people suffer from diabetes mellitus worldwide and this number could double within 15 years. Normal function of the brain is dependent on continuous supply of glucose. In hypoglycemia, production of counterregulatory hormones (glucagon, epinephrine, growth hormone, and cortisol) increases, the sympathetic system becomes stimulated, and features of neuroglycopenia appear in order to save the homeostasis. Hypoglycemia is an alarming, actually life threatening condition, but the exposure to chronic hyperglycemia has a more detrimental effect on the brain than recurrent exposure to severe hypoglycemia. The active neural response to hyperglycemia induces changes in gene expression and function. The first steps against hyperosmolality are initially adaptive, but later hyperactivation of the hypothalamic magnocellular neurosecretory cells leads to their structural damage. Changes in hippocampal gene transcription are partially implicated in the deterioration of declarative memory. Neurologically passive shunting of excess glucose through alternative cellular metabolic pathways induces atherogenic, vascular lesions, free radicals, leukoencephalopathy and atrophy of the brain and thus leading to cognitive deficits. In physiological conditions insulin has neuroprotective effect. However, insulin resistance in the central nervous system correlates with insulin resistance in the periphery. Loss of responsiveness to insulin could render neurons more susceptible to neurotoxic insults, the protective effect of insulin diminishes, and apoptosis, neurodegeneration and the resultant cognitive decline are all increased in insulin-resistant patients. Some unclear relations appear between diabetes mellitus and Alzheimer's disease. Diabetic patients with APOE-4 gene have an increased risk for Alzheimer's disease. Prevalence of depression is higher in patients with diabetes mellitus and in turn, depression is a risk factor for diabetes mellitus. Simultaneous presence of depression and diabetes mellitus tends to worsen the course of both.
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PMID:[Cerebral complications of diabetes mellitus]. 1805 61

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are the two major regulatory peptides in the hypothalamic-pituitary-adrenal (HPA) axis. Glucagon-like peptide-1 (GLP-1), an important regulator of metabolism or energy homeostasis, is implicated in the regulation of the HPA axis in response to stress and may act directly on CRF and AVP neurons. To elucidate the direct regulation of CRF and AVP genes by GLP-1 in the hypothalamus, we examined the effect of GLP-1 in hypothalamic 4B cells, which show the characteristics of hypothalamic paraventricular nucleus neurons. The mRNA of GLP-1 receptor was detected in 4B cells by RT-PCR. GLP-1 significantly stimulated both CRF and AVP mRNA levels. Cells were transfected with CRF or AVP promoter to examine the activity of each promoter. GLP-1 directly stimulated the activities of both CRF and AVP promoters in hypothalamic 4B cells. Basal promoter activities of both CRF and AVP were increased in higher glucose medium. In addition, CRF and AVP promoter activities were increased by GLP-1 in standard or low glucose medium but not in higher glucose medium. An equimolar concentration of metabolically inactive l-glucose failed to mimic the effect of d-glucose, indicating that the event was caused by changes in glucose levels and not by hyperosmolality. Together, these data suggest that GLP-1 would contribute to stress responses through activation of CRF and AVP genes in the hypothalamic cells. Hyperglycemia may be one of the stressors enhancing the syntheses of CRF and AVP in the hypothalamus.
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PMID:Action of glucagon-like peptide 1 and glucose levels on corticotropin-releasing factor and vasopressin gene expression in rat hypothalamic 4B cells. 2280 Nov 6