Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes a 6-year-old Simmental bull with diabetes mellitus. The animal was referred to our clinic because of severe weight loss and chronic indigestion. Clinical examination revealed markedly disturbed general condition, impaired forestomach function and polyuria. There was aciduria, glucosuria and ketonuria. The most important biochemical findings were severe hyperglycemia, markedly increased activities of hepatic enzymes and severe metabolic acidosis. Plasma concentrations of insulin, insulin-like growth factor-I, thyroxine and 3,5,3'-triiodothyronine were lower than normal, whereas those of glucagon were higher than normal. Based on these findings, a diagnosis (secondary) diabetes mellitus was made. The bull was slaughtered and histological examination revealed mixed cell pancreatitis with severe degeneration of islet cells. Immunohistochemical examination of the pancreas showed that very few insulin-, glucagon-, somatostatin- and pancreatic polypeptide, insulin-like growth factor-I and adrenomedullin-producing islet cells were present.
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PMID:[Diabetes mellitus caused by pancreatitis in a bull]. 1123 31

The pancreas is essential for digestion and glucose homeostasis. Diseases associated with the pancreas (e.g., pancreatitis, pancreatic cancer, diabetes) are generally debilitating for the patient. Diabetes is particularly prominent in the United States, affecting nearly 6 percent of the population, with associated annual health costs in the billions of dollars. Pancreas development is a complex process that requires the timely expression of numerous factors. Among them, a basic Helix-Loop-Helix factor, BETA2, was shown to be important for terminal differentiation of islet cells including insulin- and glucagon-producing cells. Expression studies demonstrated the presence of BETA2 in islet cells and specific neurons. Targeted deletion of the BETA2 gene in mice revealed its significance in pancreas development. In addition, BETA2 is important in granule cell development of the hippocampus and cerebellum. This chapter will focus on the role of BETA2 in pancreas physiology, neuronal development, and its molecular biology.
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PMID:BETA2 and pancreatic islet development. 1123 15

Acute pancreatitis is an acute inflammatory disease of the pancreas, with variable involvement of other regional tissues or remote organ systems. Acute pancreatitis is mild in 80% of cases; virtually all patients with this form of disease will survive, because it's associated with minimal organ dysfunction and uneventful recovery; the severe pancreatitis develops in 20% of cases and is associated with higher morbidity and mortality. It's most important to identify the severity of disease at the moment of hospital admission; many scoring systems have been developed to serve as early prognostic signs: Ranson's criteria, Imrie's criteria, Apache II score, Balthazar's TC score. Recently, new drugs have been proposed in the treatment of acute pancreatitis, as, for example, calcitonine, glucagon, systemic antioxidants, antagonists of the receptors of interleukines, antiproteases (aprotinin and gabexate-mesilate) and the inhibitors of pancreatic secretions (somatostatin and its analogues). However, many controversies still exist concerning the real efficacy of these drugs in the treatment of acute pancreatitis, particularly regarding the inhibitors of pancreatic secretions: recently, some studies showed that somatostatin is able to actually reduce the local complication of the disease and the development of severe forms of acute pancreatitis; on the other hand, other studies failed to show real advantages of somatostatin reducing morbidity and mortality for pancreatitis. The aim of present study is a retrospective analysis of patients affected by acute pancreatitis in order to evaluate efficacy of somatostatin and its analogues. All patients subdivided in two groups: group A, patients treated with conventional therapy plus somatostatin and/or octreotide (SS/LS), and group B, patients treated only with conventional therapy. Results seem to show that somatostatin does not positively affect morbidity and mortality in patients with acute pancreatitis. The Authors conclude that, at present; somatostatin cannot be considered surely effective in preventing complications and mortality in acute pancreatitis. Further studies are still necessary to verify the effectiveness of somatostatin and its analogues in the therapy of acute pancreatitis.
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PMID:[Efficacy of somatostatin and its analogues in the treatment of acute pancreatitis: clinical retrospective study]. 1137 Feb 23

Members of the TGF-beta superfamily of cytokines have been implicated in pancreatic cancer, pancreatitis and in regulation and differentiation of pancreatic endocrine and exocrine cells. Different TGF-beta members signal through phosphorylation of different signal transduction proteins, which eventually form oligomers with SMAD 4 and translocate to the nucleus. Reverse transcriptase-polymerase chain reaction showed that SMADs 1, 2 and 4 are expressed in pancreatic islets. Immunostaining revealed that SMAD 1 and 4 predominantly were expressed by islet insulin and glucagon cells. Since SMAD 1 is known to transduce signals from receptors binding bone morphogenetic protein (BMP) these results indicate a previously unknown role of BMP-like ligands in islet function.
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PMID:Expression of SMAD signal transduction molecules in the pancreas. 1168 56

The aim of the present study was to investigate the spontaneous and cholecystokinin-octapeptide (CCK-8)-promoted laboratory changes and morphological alterations in rats with arginine (Arg)-induced pancreatitis in which diabetes had been induced with streptozotocin (STZ). Male Wistar rats were used in our experiments. Pancreatitis was induced by arginine, diabetes by STZ and regeneration was promoted by CCK-8. The serum amylase, glucose and insulin levels, the pancreatic contents of protein, DNA, amylase, trypsinogen and lipase, the pancreatic weight/body- weight ratio (pw/bw) and the plasma glucagon level were examined 1, 3, 7, 14 and 28 days after pancreatitis induction. Pancreatic tissue samples were examined by light microscopy and immunostaining on paraffin-embedded sections. The insulin and glucagon-containing cells were visualized by using monoclonal antibodies. The administration of low doses of CCK-8 accelerated the processes of regeneration following Arg-induced pancreatitis, but in rats that were also diabetic, pancreatic regeneration was not observed. The administration of low doses of CCK-8 seems to reduce the pancreatic beta -cell number and function in diabetic rats. The pancreatic endocrine function was further deteriorated by simultaneous Arg-induced pancreatitis. The diabetic state appeared to shift the normal pancreatic enzyme content (decreased amylase and increased trypsinogen) in this study.
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PMID:Cholecystokinin fails to promote pancreatic regeneration in diabetic rats following the induction of experimental pancreatitis. 1171 66

Diabetes mellitus (DM) in chronic pancreatitis (ChP) is considered a unique clinical and metabolic unit. Compared to type I DM it has many different properties: glycemic lability, more frequent hypoglycaemic episodes, and minimum incidence of ketoacidosis. The need of insulin administration to achieve satisfying diabetes mellitus compensation is significantly lower and response of peripheral tissues to endogenous and exogenous insulin significantly higher compared to type I diabetics. These clinical differences result from decreased but always preserved insulin secretion, decreased glucagon production, impaired external pancreatic secretion, and also excessive alcohol use or insufficient or irregular food intake of the patients. Secondary DM in ChP is accompanied by chronic, microangiopathic and neuropathic complications analogous to other DM types. Nonpharmacological treatment measurements of the first choice are elimination of alcohol, sufficient and adequate nutrition, and simultaneous treatment of impaired exocrinal secretion. A pharmacology treatment is insulin therapy! It is a substitution treatment for insulin deficiency. Insulin doses must be chosen very carefully because of the risk of hypoglycaemia. The most frequent cause of secondary diabetes mellitus in patients with pancreatic diseases in Europe is chronic alcoholic pancreatitis and in tropical countries and India non-alcoholic tropical calcific pancreatitis (TCP).
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PMID:[Diabetes mellitus in chronic pancreatitis]. 1530 35

Diabetic ketoacidosis (DKA) is the most common hyperglycemic emergency in patients with diabetes mellitus. DKA most often occurs in patients with type 1 diabetes, but patients with type 2 diabetes are susceptible to DKA under stressful conditions, such as trauma, surgery, or infections. DKA is reported to be responsible for more than 100 000 hospital admissions per year in the US, and accounts for 4-9% of all hospital discharge summaries among patients with diabetes. Treatment of patients with DKA uses significant healthcare resources and accounts for 1 out of every 4 healthcare dollars spent on direct medical care for adult patients with type 1 diabetes in the US. Recent studies using standardized written guidelines for therapy have demonstrated a mortality rate of less than 5%, with higher mortality rates observed in elderly patients and those with concomitant life-threatening illnesses. Worldwide, infection is the most common precipitating cause for DKA, occurring in 30-50% of cases. Urinary tract infection and pneumonia account for the majority of infections. Other precipitating causes are intercurrent illnesses (i.e., surgery, trauma, myocardial ischemia, pancreatitis), psychological stress, and non-compliance with insulin therapy. The triad of uncontrolled hyperglycemia, metabolic acidosis and increased total body ketone concentration characterizes DKA. These metabolic derangements result from the combination of absolute or relative insulin deficiency and increased levels of counter-regulatory hormones (glucagon, catecholamines, cortisol, and growth hormone). Successful treatment of DKA requires frequent monitoring of patients, correction of hypovolemia and hyperglycemia, replacement of electrolyte losses, and careful search for the precipitating cause. Since the majority of DKA cases occur in patients with a known history of diabetes, this acute metabolic complication should be largely preventable through early detection, and by the education of patients, healthcare professionals, and the general public. The frequency of hospitalizations for DKA has been reduced following diabetes education programs, improved follow-up care, and access to medical advice. Novel approaches to patient education incorporating a variety of healthcare beliefs and socioeconomic issues are critical to an effective prevention program.
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PMID:Diabetic ketoacidosis: risk factors and management strategies. 1587 46

A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160,000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5- and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 +/- 0.07 and 3.36 +/- 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.
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PMID:Intramuscular autotransplantation of pancreatic islets in a 7-year-old child: a 2-year follow-up. 1809 67

The mammalian pancreas originates from two developing buds on the dorsal and ventral side of the duodenum which fuse and convert into a single mixed gland, composed of exocrine and endocrine cells. In the adult organism, the exocrine pancreas consists of acinar and ductal cells which are organised in a lobular branched tissue architecture and secrete and transport digestive enzymes into the duodenum. Mature endocrine cells, which represent only 1-2% of the pancreatic organ volume, form aggregates of so called islets of Langerhans within the exocrine pancreatic tissue and control glucose homeostasis by secretion of glucagon, insulin and other hormones into the bloodstream. Pancreatitis is the most common and a potentially lethal disorder of the exocrine pancreas with limited therapeutic options. A major obstacle in the development of successful treatment strategies has, until today, been our limited knowledge of the disease pathophysiology. This review will summarise recent advances in our understanding of the physiological mechanisms involved in the early disease processes of the exocrine pancreas.
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PMID:New advances in pancreatic cell physiology and pathophysiology. 1820 9

Oral therapy for type 2 diabetes mellitus, when used appropriately, can safely assist patients to achieve glycaemic targets in the short to medium term. However, the progressive nature of type 2 diabetes usually requires a combination of two or more oral agents in the longer term, often as a prelude to insulin therapy. Issues of safety and tolerability, notably weight gain, often limit the optimal application of anti-diabetic drugs such as sulfonylureas and thiazolidinediones. Moreover, the impact of different drugs, even within a single class, on the risk of long-term vascular complications has come under scrutiny. For example, recent publication of evidence suggesting potential detrimental effects of rosiglitazone on myocardial events generated a heated debate and led to a reduction in use of this drug. In contrast, current evidence supports the view that pioglitazone has vasculoprotective properties. Both drugs are contraindicated in patients who are at risk of heart failure. An additional recently identified safety concern is an increased risk of fractures, especially in postmenopausal women.Several new drugs with glucose-lowering efficacy that may offer certain advantages have recently become available. These include (i) injectable glucagon-like peptide-1 (GLP-1) receptor agonists and oral dipeptidyl peptidase-4 (DPP-4) inhibitors; (ii) the amylin analogue pramlintide; and (iii) selective cannabinoid receptor-1 (CB1) antagonists. GLP-1 receptor agonists, such as exenatide, stimulate nutrient-induced insulin secretion and reduce inappropriate glucagon secretion while delaying gastric emptying and reducing appetite. These agents offer a low risk of hypoglycaemia combined with sustained weight loss. The DPP-4 inhibitors sitagliptin and vildagliptin are generally weight neutral, with less marked gastrointestinal adverse effects than the GLP-1 receptor agonists. Potential benefits of GLP-1 receptor stimulation on beta cell neogenesis are under investigation. Pancreatitis has been reported in exenatide-treated patients. Pramlintide, an injected peptide used in combination with insulin, can reduce insulin dose and bodyweight. The CB1 receptor antagonist rimonabant promotes weight loss and has favourable effects on aspects of the metabolic syndrome, including the hyperglycaemia of type 2 diabetes. However, in 2007 the US FDA declined approval of rimonabant, requiring more data on adverse effects, notably depression. The future of dual peroxisome proliferator-activated receptor-alpha/gamma agonists, or glitazars, is presently uncertain following concerns about their safety.In conclusion, several new classes of drugs have recently become available in some countries that offer new options for treating type 2 diabetes. Beneficial or neutral effects on bodyweight are an attractive feature of the new drugs. However, the higher cost of these agents, coupled with an absence of long-term safety and clinical outcome data, need to be taken into consideration by clinicians and healthcare organizations.
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PMID:New drugs for type 2 diabetes mellitus: what is their place in therapy? 1884 4


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