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)

Diabetes mellitus and heart failure (HF) commonly coexist, and together these conditions are associated with increased morbidity and mortality compared with either condition alone. Although the optimal treatment strategy to achieve glucose control in HF patients with type 2 diabetes has not been well studied, given the common coexistence of these conditions and the need to adequately treat hyperglycemia to prevent microvascular complications, it is important for clinicians to understand the potential implications of diabetic therapy in patients with established HF. Until recently, metformin was contraindicated in patients with HF because of the potential risk of lactic acidosis; however, recent retrospective studies of metformin use in HF patients have shown that this medication may be used safely and indeed may be beneficial in patients with stable HF. The association between thiazolidinediones (TZDs) and HF remains controversial, but recent prospective randomized trials of TZD use in HF patients suggest that worsening volume retention associated with these agents may lead to worsening of HF symptoms. The recently developed incretin-based therapies, such as exenatide and sitagliptin, also have not been extensively studied in HF populations; however, small pilot studies of glucagon-like peptide-1 have shown potential promise in the treatment of diabetic patients with HF. Although they may be difficult to perform, future randomized controlled trials are needed to establish optimal treatment goals and strategies in this population.
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PMID:Management of type 2 diabetes in patients with heart failure. 1902 77

Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM) comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1), the dipeptidyl peptidase 4 (DPP-4) inhibitors, dual peroxisome proliferator-activated receptors (PPAR) agonists (glitazars) and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD). Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM. Summarizing the present information it can be stated that 1. Four out the five classical oral antidiabetic drug groups present proven or potential cardiac hazards; 2. These hazards are not mere 'side effects', but biochemical phenomena which are deeply rooted in the drugs' mechanism of action; 3. Current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of T2DM with proven CAD; 4. Glitazones should be avoided in patients with overt heart failure; 5, The novel incretin mimetic drugs and DPP-4 inhibitors--while usually inadequate as monotherapy--appear to be satisfactory adjuvant drugs due to the lack of known undesirable cardiovascular effects; 6. Customized antihyperglycemic pharmacological approaches should be implemented for the achievement of optimal treatment of T2DM patients with heart disease. In this context, it should be carefully taken into consideration whether the leading clinical status is CAD or heart failure.
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PMID:A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease. 1961 27

Type 2 diabetes is a complex disease with the coexistence of several pathophysiological abnormalities such as a defect of insulin secretion, a relative hyperglucagonaemia, an increased hepatic glucose production and a muscular insulin resistance. In order to tackle all these abnormalities, the coadministration of several drugs with complementary actions is frequently required. Janumet is a fixed-dose combination of sitagliptin, a specific inhibitor of dipeptidylpeptidase-4 that blocks the rapid degradation of so-called incretin hormones (resulting in a potentiation of insulin secretion and reduction of glucagon secretion in a glucose-dependent manner), and of metformin, a biguanide compound that reduces glucose hepatic production and slightly improves insulin sensitivity. This pharmacological combination improves glucose control without inducing hypoglycaemia or weight gain. The tolerance profile is rather good, with (digestive) side effects and contraindications (risk of lactic acidosis in case of renal insufficiency) attributable to metformin. Janumet (50/850 mg or 50/1.000 mg), twice daily, is indicated in the treatment of type 2 diabetes and is currently reimbursed in Belgium after failure of metformin monotherapy or the prior demonstration of the efficacy of adding sitaglitptin (Januvia) to metformin.
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PMID:[Medication of the month. Sitagliptin-metformin fixed combination (Janumet)]. 2118 32

A 14-month-old female infant presented with recurrent episodes of acute gastroenteritis accompanied by severe metabolic acidosis and hypoglycemia. Physical examination showed hepatomegaly. Laboratory evaluation revealed elevated hepatic enzymes, prolonged prothrombin time, hyperuricemia, and extremely elevated lactate and alanine levels. Glucagon injection during hypoglycemia resulted in a further decrease of blood glucose. She was treated with glucose-containing intravenous fluids, with rapid improvement and normalization of her blood pH and glucose levels. Hormonal assessment during two episodes of hypoglycemia indicated growth hormone (GH) deficiency. However, as isolated GH deficiency could not explain all other concomitant features, such as severe lactic acidosis, hepatomegaly, impaired liver function, and hyperuricemia, the possibility of a combined defect was suggested. Further lymphocytic enzymatic investigation revealed fructose-1,6-diphosphatase deficiency and molecular genetic analysis demonstrated frame shift mutation in the FBP1 gene. This enzyme deficiency causes a rare metabolic disorder not previously described in combination with GH deficiency.
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PMID:Recurrent infantile hypoglycemia due to combined fructose-1,6-diphosphatase deficiency and growth hormone deficiency. 2358 10

Hyperglycemia affects approximately one-third of acute ischemic stroke patients and is associated with poor clinical outcomes. In experimental and clinical stroke studies, hyperglycemia has been shown to be detrimental to the penumbral tissue for several reasons. First, hyperglycemia exacerbates both calcium imbalance and the accumulation of reactive oxygen species (ROS) in neurons, leading to increased apoptosis. Second, hyperglycemia fuels anaerobic energy production, causing lactic acidosis, which further stresses neurons in the penumbral regions. Third, hyperglycemia decreases blood perfusion after ischemic stroke by lowering the availability of nitric oxide (NO), which is a crucial mediator of vasodilation. Lastly, hyperglycemia intensifies the inflammatory response after stroke, causing edema, and hemorrhage through disruption of the blood brain barrier and degradation of white matter, which leads to a worsening of functional outcomes. Many neuroprotective treatments addressing hyperglycemia in stroke have been implemented in the past decade. Early clinical use of insulin provided mixed results due to insufficiently controlled glucose levels and heterogeneity of patient population. Recently, however, the latest Stroke Hyperglycemia Insulin Network Effort trial has addressed the shortcomings of insulin therapy. While glucagon-like protein-1 administration, hyperbaric oxygen preconditioning, and ethanol therapy appear promising, these treatments remain in their infancy and more research is needed to better understand the mechanisms underlying hyperglycemia-induced injuries. Elucidation of these mechanistic pathways could lead to the development of rational treatments that reduce hyperglycemia-associated injuries and improve functional outcomes for ischemic stroke patients.
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PMID:Hyperglycemia in stroke and possible treatments. 2362 37

The human small intestine is organized with a proximal-to-distal gradient of mucosal structure and nutrient processing capacity. However, certain nutrients undergo site-specific digestion and absorption, such as iron and folate in the duodenum/jejunum vs vitamin B12 and bile salts in the ileum. Intestinal resection can result in short bowel syndrome (SBS) due to reduction of total and/or site-specific nutrient processing areas. Depending on the segment(s) of intestine resected, malabsorption can be nutrient specific (eg, vitamin B12 or fat) or sweeping, with deficiencies in energy, protein, and various micronutrients. Jejunal resections are generally better tolerated than ileal resections because of greater postresection adaptive capacity than that of the jejunum. Following intestinal resection, energy scavenging and fluid absorption become particularly important in the colon owing to loss of digestive and absorptive surface area in the resection portion. Resection-induced alterations in enteroendocrine cell abundance can further disrupt intestinal function. For example, patients with end jejunostomy have depressed circulating peptide YY and glucagon-like peptide 2 concentrations, which likely contribute to the rapid intestinal transit and blunted intestinal adaptation observed in this population. SBS-associated pathophysiology often extends beyond the gastrointestinal tract, with hepatobiliary disease, metabolic bone disease, D-lactic acidosis, and kidney stone formation being chronic complications. Clinical management of SBS must be individualized to account for the specific nutrient processing deficit within the remnant bowel and to mitigate potential complications, both inside and outside the gastrointestinal tract.
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PMID:Pathophysiology of short bowel syndrome: considerations of resected and residual anatomy. 2450 Sep 9

Diabetic emergencies are common presentations to the emergency department. It is estimated that diabetes affects 25.8 million people in the United States, at an annual total cost of over $174 billion. There are 2 general categories of diabetic emergencies: hyperglycemic and hypoglycemic. The hyperglycemic emergencies include diabetic ketoacidosis and hyperosmolar hyperglycemic state. Management of these conditions requires a careful hydration strategy to restore volume and improve perfusion, intravenous insulin therapy, and electrolyte monitoring. Management of hypoglycemia includes identification of the underlying etiology, oral food and/or glucose, intravenous dextrose, and consideration of glucagon. This review evaluates the current strategies for management of diabetic emergencies and offers new information regarding effective diagnostic strategies, selection of fluids for rehydration, correction of potassium, the use of subcutaneous insulin for mild hyperglycemia, and management of metformin-induced lactic acidosis.
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PMID:Diabetic emergencies: new strategies for an old disease. 2529 33

Metformin, a biguanide, is considered in EASD and ADA to be a first-line glucose-lowering agent for patients with type 2 diabetes. The effectiveness of metformin as an anti-diabetic drug is explained by its ability to lower blood glucose by decreasing hepatic glucose production, stimulating glucose uptake in the muscle, and increasing fatty acid oxidation in adipose tissue. The exact mechanism of this effect has not been fully understood, but metformin is thought to activate hepatic AMP-activated protein kinase (AMPK), and it suppresses liver glucagon signal by increasing AMP due to inhibition of mitochondrial respiratory complex I. Caution is advised to avoid use of metformin in patients at risk for lactic acidosis (e.g., in patients with advanced renal and liver insufficiency, infection, dehydration, alcoholism, or in those using diuretics or SGLT2 inhibitor).
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PMID:[Biguanide]. 2581 64

About 80% of patients with liver cirrhosis may have glucose metabolism disorders, 30% show overt diabetes mellitus (DM). Prospective studies have demonstrated that DM is associated with an increased risk of hepatic complications and death in patients with liver cirrhosis. DM might contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochondrial oxidative stress mediated by adipokines. Based on the above mentioned the effective control of hyperglycemia may have a favorable impact on the evolution of these patients. However, only few therapeutic studies have evaluated the effectiveness and safety of antidiabetic drugs and the impact of the treatment of DM on morbidity and mortality in patients with liver cirrhosis. In addition, oral hypoglycemic agents and insulin may produce hypoglycemia and lactic acidosis, as most of these agents are metabolized by the liver. This review discusses the clinical implications of DM in patients with chronic liver disease. In addition the effectiveness and safety of old, but particularly the new antidiabetic drugs will be described based on pharmacokinetic studies and chronic administration to patients. Recent reports regarding the use of the SGLT2 inhibitors as well as the new incretin-based therapies such as injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral inhibitors of dipeptidylpeptidase-4 (DPP-4) will be discussed. The establishment of clear guidelines for the management of diabetes in patients with CLD is strongly required.
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PMID:The treatment of diabetes mellitus of patients with chronic liver disease. 2684 9


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