Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One form of maturity-onset diabetes of the young, Type 3 (MODY3), results from mutations in the gene coding for hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor first described in the liver. MODY3 is characterized by a defective glucose-stimulated insulin secretion. Earlier observations of glycosuria with normal blood glucose levels in some MODY families suggest an additional renal manifestation of the respective genetic defect. We measured the renal threshold for glucose in five diabetic carriers of a missense mutation (Arg 272 His) in HNF-1alpha and, for comparison, in eight Type 1 diabetic patients, applying a non-invasive protocol of frequent parallel blood and urine sampling during a slow shift in blood glucose levels. We found that the mean renal threshold for glucose was lowered in the HNF-1alpha diabetic patients compared to those with Type 1 diabetes (6.5 +/- 0.9 mmol l(-1) vs 10.7 +/- 0.5 mmol l(-1); p < 0.01). This lowered glucose threshold might be an indication of an extra-pancreatic effect of HNF-1alpha gene mutations in humans. Defects in HNF-1alpha may lead to an altered tubular glucose reabsorption, possibly due to decreased expression of the renal glucose transporter proteins involved in reabsorption of glucose from the urine.
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PMID:A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene. 979 80

A 70-year-old man is referred to a urologist for recommendations on the management of metastatic prostate cancer. His cancer was diagnosed 5 years ago, and he underwent radical prostatectomy at that time. The tumour was confined to the prostate gland (Gleason score 7), and during surgery the lymph nodes were assessed as being clear of cancer. Before the surgery, the patient's prostate-specific antigen (PSA) level had been 8 ng/mL. After the prostatectomy, PSA was at first undetectable, but recently the PSA level rose to 2 ng/mL and then, at the most recent test, to 16 ng/mL. A bone scan was ordered to investigate back discomfort, which has been persistent but easily controlled with acetaminophen. Unfortunately, the bone scan shows several sites of metastatic disease. The man's medical history includes type 2 diabetes, which has developed during the past 3 years and which is controlled by diet, as well as asymptomatic hypertension, which is managed by means of a thiazide diuretic. The patient asks what treatments are available, what impact they are likely to have on his disease and what risks are associated with the therapies.
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PMID:Prostate cancer: 9. Treatment of advanced disease. 995 46

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and improves glycemic control in type 2 diabetes. In serum the peptide is degraded by dipeptidyl peptidase IV (DPP IV). The resulting short biological half-time limits the therapeutic use of GLP-1. DPP IV requires an intact alpha-amino-group of the N-terminal histidine of GLP-1 in order to perform its enzymatic activity. Therefore, the following GLP- analogues with alterations in the N-terminal position 1 were synthesized: N-methylated- (N-me-GLP-1), alpha-methylated (alpha-me-GLP-1), desamidated- (desamino-GLP-1) and imidazole-lactic-acid substituted GLP-1 (imi-GLP-1). All GLP-1 analogues except alpha-me-GLP-1 were hardly degraded by DPP IV in vitro. The GLP-1 analogues showed receptor affinity and in vitro biological activity comparable to native GLP-1 in RINm5F cells. GLP-1 receptor affinity was highest for imi-GLP-1, followed by alpha-me-GLP-1 and N-me-GLP-1. Only desamino-GLP-1 showed a 15-fold loss of receptor affinity compared to native GLP-1. All analogues stimulated intracellular cAMP production in RINm5F cells in concentrations comparable to GLP-1. N-terminal modifications might therefore be useful in the development of long-acting GLP-1 analogues for type 2 diabetes therapy.
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PMID:GLP-1-analogues resistant to degradation by dipeptidyl-peptidase IV in vitro. 1067 9

A 45-year-old man had been complaining of thirst and polydypsia for the last 3 months and was diagnosed as having type 2 diabetes mellitus because his fasting blood glucose showed 221 mg/dl with positive urinary ketone. He was hospitalized to a private hospital and Penfil 30R was started. However, serum gamma-GTP and aminotransferases began to elevate after insulin treatment and exceeded 1000 IU/l. Insulin was discontinued and serum gamma-GTP and aminotransferases returned close to the normal range. Since his glycemic control became poor again, Penfil 30R was restarted and serum gamma-GTP and aminotransferases elevated again. Therefore, insulin was discontinued and the patient was referred to the Third Department of Internal Medicine, Yamanashi Medical University Hospital because of liver dysfunction. His plasma glucose decreased by diet therapy, and improved further by the administration of glibenclamide. After obtaining informed consent, Humalin R was challenged. Seven days after insulin injection, serum aminotransferases began to elevate again. Lymphocyte stimulation test was negative against three preparations (Penfil R, Penfil N and Humalin R). The present case suggests that human insulin itself can cause liver dysfunction and we need to pay more attention to liver function tests when we start insulin treatment.
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PMID:A type 2 diabetic patient with liver dysfunction due to human insulin. 1080 59

A 60-year-old man reported chest pain and shortness of breath. His medical history was negative for myocardial infarction but positive for "mini strokes" and type 2 diabetes mellitus. Tc-99m sestamibi cardiac imaging revealed an abnormal focus of increased activity in the left lobe of the thyroid. Although no cardiac abnormalities were found, a I-123 thyroid scan subsequently showed a solitary hypofunctioning nodule involving the middle and inferior aspects of the left lobe of the thyroid, which fine-needle aspiration proved was a Hurthle cell carcinoma.
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PMID:Incidental detection of a malignant hurthle cell carcinoma by Tc-99m sestamibi cardiac imaging. 1083 98

The peroxisome proliferator activated receptors-gamma (PPARgamma) belong to the superfamily of nuclear transcription factors acting as master genes regulating events in adipocyte differentiation. Thus, PPARgamma is a candidate gene for affecting insulin sensitivity and the pathogenesis of insulin resistance. PPARs trigger endocrine response of two important adipose tissue-derived signalling factors, leptin and tumor necrosis factor-alpha. Leptin is the afferent signal in a negative feedback loop regulating adipose tissue mass and energy balance. It generates insulin-like signals for glucose transport and glycogen synthesis via leptin receptors and the PI3-kinase and could, therefore, play a role as a mediator of obesity-related insulin resistance. Recently, a silent substitution in the coding sequence of the PPARgamma2 gene, leading to the substitution of a C by a T in exon 6 (nt 161), was described. In a recent study, it was proposed that mutations in PPARgamma could play a role in individuals who are at increased risk for developing obesity and type 2 diabetes mellitus by influencing leptin levels. We therefore examined the prevalence of the CAC(His) --> CAT(His) mutation in non-diabetic first degree relatives of subjects with type 2 diabetes to determine a possible association of this mutation to leptin levels and insulin sensitivity. 138 probands were characterised by oral glucose tolerance tests, euglycemic-hyperinsulinemic glucose-clamp and by measuring leptin levels. We found 93 (67.4%) probands without the CAC(His) --> CAT(His) substitution and 45 heterozygotes (36.6%). When the whole group was analysed for an association of the mutation with plasma leptin concentration and insulin sensitivity, no statistical significance could be demonstrated. Independently of the mutation, leptin levels were significantly (p<0.001) higher in female subjects.
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PMID:The silent PPARgamma exon 6 CAC(His) --> CAT(His) polymorphism does not affect the plasma leptin levels in a collective of first degree relatives of type 2 diabetes patients from South West Germany. 1098 52

Chronic renal failure is an unusual complication of hereditary clotting disorders (HCDs), but this situation could change in the near future. The modality of dialysis for end-stage renal disease (ESRD) in patients with an HCD is a difficult choice. Hemodialysis (HD) may be considered, but intensive treatment with coagulation factors is required for vascular access execution and for each HD procedure. Peritoneal dialysis (PD) has been infrequently proposed. However, PD requires coagulation replacement therapy only during peritoneal catheter placement. The aim of this paper is to describe our experience of three patients with ESRD and HCD, successfully treated with chronic PD in the medium term. Case 1 was a 58-year-old man with moderate hemophilia A, type 2 diabetes mellitus, and hepatitis C virus (HCV) infection. His ESRD was secondary to glomerulonephritis. A double-cuff peritoneal catheter was surgically placed with pre-emptive factor VIII administration. He began treatment with continuous ambulatory peritoneal dialysis (CAPD). An inguinal hernia was repaired without complications. After eleven months of follow-up, no hemorrhage episodes have been observed and clinical outcome is optimal. Case 2 was a 46-year-old man with severe hemophilia A, type 2 diabetes mellitus, and HCV and human immunodeficiency virus (HIV) infections. He developed a diabetic nephropathy that required renal replacement therapy. A permanent silicone catheter was inserted in the left internal jugular vein, and the patient started HD treatment. Later on, PD therapy was proposed. A peritoneal catheter was implanted with simultaneous factor VIII infusion. Minimal bleeding was observed at the subcutaneous tunnel over the following 48 hours. The patient started PD treatment without complications, and two months later, remaining asymptomatic, transferred to another center. Case 3 was a 41-year-old woman diagnosed with von Willebrand disease type 2A, HCV infection, and polycystic kidney disease, who presented with ESRD. An internal arteriovenous fistula was performed under coagulation factor cover. During a fistulography, and despite coagulation factor substitutive treatment, the patient showed an important hematoma. Afterwards, PD was considered. A peritoneal catheter was implanted under coagulation factor cover. The postoperative course was uncomplicated, and the patient started CAPD treatment. During follow up, she suffered two hemoperitoneum episodes that were resolved with cold dialysate. After nine months, she uneventfully continued on PD. In conclusion, PD is the therapy of choice for patients with hereditary clotting disorders and ESRD requiring dialysis. Peritoneal dialysis therapy avoids many of the complications related to HD therapy.
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PMID:Peritoneal dialysis is the therapy of choice for end-stage renal disease patients with hereditary clotting disorders. 1104 86

Glucagon-like peptide-1(7-36)amide (tGLP-1) has attracted considerable potential as a possible therapeutic agent for type 2 diabetes. However, tGLP-1 is rapidly inactivated in vivo by the exopeptidase dipeptidyl peptidase IV (DPP IV), thereby terminating its insulin releasing activity. The present study has examined the ability of a novel analogue, His(7)-glucitol tGLP-1 to resist plasma degradation and enhance the insulin-releasing and antihyperglycemic activity of the peptide in 20-25-week-old obese diabetic ob/ob mice. Degradation of native tGLP-1 by incubation at 37 degrees C with obese mouse plasma was clearly evident after 3 h (35% intact). After 6 h, more than 87% of tGLP-1 was converted to GLP-1(9-36)amide and two further N-terminal fragments, GLP-1(7-28) and GLP-1(9-28). In contrast, His(7)-glucitol tGLP-1 was completely resistant to N-terminal degradation. The formation of GLP-1(9-36)amide from native tGLP-1 was almost totally abolished by addition of diprotin A, a specific inhibitor of DPP IV. Effects of tGLP-1 and His(7)-glucitol tGLP-1 were examined in overnight fasted obese mice following i.p. injection of either peptide (30 nmol/kg) together with glucose (18 mmol/kg) or in association with feeding. Plasma glucose was significantly lower and insulin response greater following administration of His(7)-glucitol tGLP-1 as compared to glucose alone. Native tGLP-1 lacked antidiabetic effects under the conditions employed, and neither peptide influenced the glucose-lowering action of exogenous insulin (50 units/kg). Twice daily s.c. injection of ob/ob mice with His(7)-glucitol tGLP-1 (10 nmol/kg) for 7 days reduced fasting hyperglycemia and greatly augmented the plasma insulin response to the peptides given in association with feeding. These data demonstrate that His(7)-glucitol tGLP-1 displays resistance to plasma DPP IV degradation and exhibits antihyperglycemic activity and substantially enhanced insulin-releasing action in a commonly used animal model of type 2 diabetes.
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PMID:Degradation and glycemic effects of His(7)-glucitol glucagon-like peptide-1(7-36)amide in obese diabetic ob/ob mice. 1111 Oct 14

We report on a 33-year-old patient from Sri Lanka who had been suffering from recurrent episodes of abdominal cramps since he was ten years old. He additionally suffered from postprandial flatulence and an increased frequency of bowel movements. By the age of 24, his condition had worsened with polyuria and polydipsia and he was diagnosed with type II diabetes mellitus. Recently, the patient's compliance deteriorated steadily and his diabetes mellitus was uncontrolled. His flatulence continued and he had six to seven bowel movements daily. He presented to us with renewed bouts of severe stomach cramps, similar to the painful episodes that the patient experienced in his youth. After exclusion of other etiologies and judging by the clinical picture, the patient's origin and the sonographically and radiologically verified pancreatic calcification, we rendered the diagnosis of a tropic calcifying pancreatitis with secondary diabetes mellitus. According to the literature, malignant neoplasia may develop on the basis of this disease. However, we were able to rule out a carcinoma as the cause of the current pain episodes in this patient based on clinical findings and course. We attributed the stomach cramps to compression of the common bile duct by the fibrotic head of pancreas. Pain and cholestasis regressed, thus obviating the need for surgical intervention (pancreaticojejunostomy). On therapy with enzyme substitution and insulin, the patient's exo- and endocrine pancreatic insufficiency was asymptomatic.
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PMID:[Chronic abdominal pain in a young diabetic patient]. 1111 10

Islet amyloid deposits are a characteristic pathologic lesion of the pancreas in type 2 diabetes and are composed primarily of the islet beta cell peptide islet amyloid polypeptide (IAPP or amylin) as well as the basement membrane heparan sulfate proteoglycan perlecan. Impaired processing of the IAPP precursor has been implicated in the mechanism of islet amyloid formation. The N- and C-terminal cleavage sites where pro-IAPP is processed by prohormone convertases contain a series of basic amino acid residues that we hypothesized may interact with heparan sulfate proteoglycans. This possibility was tested using affinity chromatography by applying synthetic fragments of pro-IAPP to heparin-agarose and heparan sulfate-Sepharose. An N-terminal human pro-IAPP fragment (residues 1-30) was retained by both heparin-agarose and heparan sulfate-Sepharose, eluting at 0.18 m NaCl at pH 7.5. Substitution of alanine residues for two basic residues in the N-terminal cleavage site abolished heparin and heparan sulfate binding activity. At pH 5.5, the affinity of the wild-type peptide for heparin/heparan sulfate was increased, implying a role for histidine residues at positions 6 and 28 of pro-IAPP. A C-terminal pro-IAPP fragment (residues 41-67) had no specific affinity for either heparin or heparan sulfate, and the N- or C-terminal fragments had only weak affinity for chondroitin sulfate. These data suggest that monomeric N-terminal human pro-IAPP contains a heparin binding domain that is lost during normal processing of pro-IAPP.
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PMID:Identification of a heparin binding domain in the N-terminal cleavage site of pro-islet amyloid polypeptide. Implications for islet amyloid formation. 1114 57


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