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)

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.
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PMID:Somatostatin release in response to glucose is impaired in chronic renal failure. 975 17

Food intake is regulated by short-term satiety factors (gastric distension, amino acids, peptide hormones), as well as factors involved in long-term appetite regulation (leptin, insulin). Integration of the various signals takes place in the central nervous system (CNS). Appetite suppression in uremia is multifactorial and may include effects of uremia per se and of various comorbidity and psychosocial factors. Uremic anorexia is associated with elevated levels in plasma and CNS of short-term satiety factors (cholecystokinine, glucagon, serotonin, middle molecules) and factors that influence long-range regulation of appetite (leptin, insulin), but it is still unsettled to what extent these factors cause or contribute to appetite loss in uremic patients. Proinflammatory cytokines most probably also have a role in appetite suppression and malnutrition in patients with chronic renal failure.
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PMID:Mechanisms of uremic suppression of appetite. 1043 Oct 31

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.
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PMID:Effect of octreotide on insulin requirement, hepatic glucose production, growth hormone, glucagon and c-peptide levels in type 2 diabetic patients with chronic renal failure or normal renal function. 1113 81

Content of gastrointestinal hormones (gastrin, insulin, glucagon, C-peptide), beta2-microglobulin, glomerular filtration rate (GFR) were studied in 65 patients with nephrolithiasis (NL) and in 73 patients with chronic renal failure (CRF). It was found that NL with GFR under 80 ml/min runs with elevated insulin, glucagon and C-peptide while CRF with CRF under 30 ml/min is characterized by aggravated disorders of hormonal homeostasis (gastrin, insulin, glucagons, C-peptide elevation). As gastrointestinal hormones in patients with CRF are high, it is recommended to combine medication with diet containing low amount of carbohydrates easy for digestion which is important in the treatment of CRF.
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PMID:[Gastrointestinal hormones in the blood serum of patients with chronic renal failure]. 1556 Jan 65

Various metabolic events may lead to dermatologic pathology. Three illustrative examples are glucagonoma syndrome, uremic pruritus, and zinc deficiency. The glucagonoma syndrome, resulting from a glucagon secreting-tumor, is characterized by a distinctive dermatitis, necrolytic migratory erythema. This skin rash is a generalized, pruritic eruption which first appears as erythematous patches, then progresses to form superficial vesicles and bullae. Uremic pruritus is a clinical phenomenon seen in patients with chronic renal failure; it provokes vigorous scratching and may lead to numerous cutaneous lesions including extensive excoriations, lichen simplex chronicus, prurigo nodularis, keratotic papules, or secondary impetigo. Zinc deficiency may be evident as an inherited disease called acrodermatitis enteropathica, which presents clinically with a predominately acral and periorificial rash of sharply demarcated erythematous, exfoliative, and exudative patches. It may also result from an acquired defect with similar clinical findings. A brief review concerning the etiology, clinical manifestations, diagnosis, and treatment are given for glucagonoma syndrome, uremic pruritus, and zinc deficiency. Any pathophysiologic dysfunction that results in a loss of metabolic control of homeostasis in the body may demonstrate cutaneous manifestations. These skin findings may be of great clinical significance and may aid in the diagnosis or even be the first sign of a disease process. The glucagonoma syndrome, uremic pruritus, and zinc deficiency are three examples of dermatologic correlates of metabolic events.
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PMID:Dermatologic correlates of selected metabolic events. 1731 68

The progressive decline of glomerular filtration rate in chronic kidney disease patients is associated with a significant reduction in food intake. Approximately one third of chronic dialysis patients complain of a fair or poor appetite and this is related directly to poor patient outcomes. Appetite regulation involves the gastrointestinal tract (ghrelin as an appetite stimulant, and cholecystokinin, glucagon-like peptide-1, and neuropeptide YY as appetite inhibitors); the adipose tissue with leptin, a potent appetite inhibitor; the vagal system; and the brain, which integrates the stimuli in the hypothalamus area. Satiety relies on the melanocortin receptors with serotonin as the main neurotransmitter and is challenged with hunger peptides, namely, neuropeptide Y and agouti-related peptide. In nondialyzed chronic renal failure patients and in maintenance dialysis patients, anorexia is related mainly to the accumulation of unidentified anorexigenic compounds, inflammatory cytokines, and alterations in appetite regulation, such as amino acid imbalance, which increases the transport of free tryptophan across the blood-brain barrier. This creates a hyperserotoninergic state that is prone to low appetite. Treatment of anorexia involves counseling, starting dialysis treatments in uremic chronic kidney disease patients, increasing the dialysis dose, and possibly using appetite stimulants.
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PMID:Why are chronic kidney disease patients anorexic and what can be done about it? 1912 70

Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.
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PMID:Renal and cardiac effects of DPP4 inhibitors--from preclinical development to clinical research. 2294 20

Glucagon-like peptide-1 (GLP-1) receptor agonists result in greater improvements in glycemic control than placebo and promote weight loss with minimal hypoglycemia in patients with type 2 diabetes mellitus. A number of case reports show an association of GLP-1 receptor agonists, mainly exenatide, with the development of acute kidney injury. The present review aims to present the available data regarding the effects of GLP-1 receptor agonists on renal function, their use in subjects with chronic renal failure and their possible association with acute kidney injury. Based on the current evidence, exenatide is eliminated by renal mechanisms and should not be given in patients with severe renal impairment or end stage renal disease. Liraglutide is not eliminated by renal or hepatic mechanisms, but it should be used with caution since there are only limited data in patients with renal or hepatic impairment. There is evidence from animal studies that GLP-1 receptor agonists exert protective role in diabetic nephropathy with mechanisms that seem to be independent of their glucose-lowering effect. Additionally, there is evidence that GLP-1 receptor agonists influence water and electrolyte balance. These effects may represent new ways to improve or even prevent diabetic nephropathy.
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PMID:Effects of glucagon-like peptide-1 receptor agonists on renal function. 2414 3

In health hypoglycaemia is rare and occurs only in circumstances like extreme sports. Hypoglycaemia in type 1 Diabetes (T1D) and advanced type 2 Diabetes (T2D) are the result of interplay between absolute or relative insulin access and defective glucose counterregulation. The basic mechanism is, failure of decreasing insulin and failure of the compensatory increasing counterregulatory hormones at the background of falling blood glucose. Any person with Diabetes on anti-diabetic medication who behaves oddly in any way whatsoever is hypoglycaemic until proven otherwise. Hypoglycaemia can be a terrifying experience for a patient with Diabetes. By definition, hypoglycaemic symptoms are subjective and vary from person to person and even episode to episode in same person. Fear of iatrogenic hypoglycaemia is a major barrier in achieving optimum glycaemic control and quality of life which limits the reduction of diabetic complications. Diabetes patients with comorbidities especially with chronic renal failure, hepatic dysfunction, major limb amputation, terminal illness, cognitive dysfunction etc. are more vulnerable to hypoglycaemia. In most cases, prompt glucose intake reverts hypoglycaemia. Exogenous insulin in T1D and insulin treated advanced T2D have no control by pancreatic regulation. Moreover, failure of increase of glucagon and attenuated secretion in epinephrine causes the defective glucose counterregulation. In this comprehensive review, I will try to touch all related topics for better understanding of hypoglycaemia.
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PMID:Hypoglycaemia. 3240 22


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