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)

This study was designed to investigate the effect of glucogon-like peptide-1 (GLP-1) on pancreatic beta-cell function in normal, Zucker diabetic fatty (ZDF) rats, a model for non-insulin-dependent diabetes mellitus (NIDDM or type II diabetes) and their heterozygous siblings. Pancreas perfusion and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes in insulin release under fasting and hyperglycemic conditions and following stimulation with GLP-1. Animals from the ZDF/Gmi-fa rats (ZDF) were grouped according to age, sex, and phenotype (obese or lean), and compared with LA lean rats. Glucose stimulation (10 mmol/L) in obese rats showed repressed response in insulin release. Glucose plus GLP-1 stimulation caused increased insulin release in all groups. The degree of this response differed between groups: lean > obese; young > adult; female > male. The LA lean control group was most sensitive, while the ZDF overtly diabetic group had the lowest response. In addition, the pulsatile pattern of insulin secretion was suppressed in ZDF rats, especially in obese groups. These results support the hypothesis that GLP-1 can effectively stimulate insulin secretion. Insulin release was defective in ZDF obese rats and could be partially restored with GLP-1. ZDF lean rats also showed suppression of beta-cell function and there was a difference in beta-cell function related to sex in ZDF strain. This study documents the efficacy of GLP-1 to stimulate insulin release and contributes to our understanding of the pathophysiological mechanisms underlying NIDDM.
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PMID:The effect of glucose and glucagon-like peptide-1 stimulation on insulin release in the perfused pancreas in a non-insulin-dependent diabetes mellitus animal model. 975 Dec 30

As a major counterregulatory hormone of insulin, glucagon plays an important role in regulating glucose homeostasis through its binding to the glucagon receptor. Recently a missense mutation in the glucagon-receptor gene (Gly40Ser) was found to be associated with type 2 diabetes in France and Sardinia, with a frequency as high as 4.6% and 8.3%, respectively. This mutation was also found to be associated with essential hypertension in the white population with a frequency of 5.4%. To investigate the role of this mutation in the pathogenesis of type 2 diabetes and essential hypertension in Taiwanese population, we screened 121 normal controls, 213 unrelated subjects with type 2 diabetes, and 107 unrelated subjects with essential hypertension by use of polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). None of the Taiwanese subjects recruited in the study had this receptor mutation. Our results demonstrate a strong genetic heterogeneity among the ethnic group and suggest that the Gly40Ser mutation of the glucagon receptor gene plays little role, if any, in the pathogenesis of type 2 diabetes and essential hypertension in the Taiwanese population.
Pancreas 1999 Mar
PMID:Screening for the Gly40Ser mutation in the glucagon receptor gene among patients with type 2 diabetes or essential hypertension in Taiwan. 1009 Apr 12

To investigate pancreatic histopathology in relation to islet function in type 2 diabetes, pancreatic tissue was examined at disease onset and after death in the genetically diabetic Chinese hamster CHIG/Han subline. The pancreatic islets displayed vacuolation, intraislet fibrosis, variable stages of degranulation, and beta-cell necrosis, but no insulitis. These lesions were associated with changes in immunostaining of major islet peptides, impaired glucose-stimulated (10 mM) insulin secretion, reduced islet insulin content, and the severity of hyperglycemia. The exocrine pancreas was characterized by peri- and intrapancreatic fat and mononuclear cell infiltration. Biopsy of the pancreas had a marked effect on plasma glucose such that at 2 weeks after excision, in 9 and 18% of the severely hyperglycemic hamsters, plasma glucose levels decreased to <7.2 and 15 mM, respectively, and 45% of the mildly hyperglycemic hamsters became transiently normoglycemic (<7.2 mM). The results showed that insulitis is not involved in beta-cell failure of diabetic CHIG/Han hamsters. Vacuolation of islets was the most prominent lesion associated with a functional islet abnormality and development of hyperglycemia. Attenuation of hyperglycemia after biopsy suggests that the pancreas, in type 2 diabetes, maintains the ability to respond to impairment with amelioration of the diabetic state.
Pancreas 1999 Jul
PMID:Relationship between the histopathology of the endocrine-exocrine pancreas parenchyma and beta-cell function in the Chinese hamster CHIG/Han subline. 1041 98

Diabetes mellitus secondary to chronic pancreatitis is characterized by a progressive destruction of the pancreas, including loss of the islet cells, leading to a form of diabetes that can mimic both type 1 and type 2 diabetes. Glucagon-like peptide 1(7-36)amide (GLP-1), an intestinally derived insulinotropic hormone, represents a potential therapeutic agent for type 2 diabetes, because exogenous GLP-1 has been shown to increase the insulin and reduce the glucagon concentrations in these patients, and thus induce lower blood glucose, but without causing hypoglycemia. Ten patients with diabetes mellitus secondary to chronic pancreatitis and five normal subjects were studied. Nine patients were treated with insulin and one patient with sulfonylurea. In the fasting state, saline or GLP-1 in doses of 0.4 or 1.2 pmol/min/kg body weight were infused intravenously for 4 hours. Blood glucose was reduced in all patients with both doses of GLP-1; plasma C-peptide increased (p<0.02), and plasma glucagon decreased (p<0.02) compared with basal levels, also in three patients with normoglycemia and high levels of presumably exogenous insulin. Similar results were obtained in the normal subjects. In conclusion, GLP-1 treatment may be considered in patients with diabetes mellitus secondary to chronic pancreatitis, provided that a certain amount of alpha- and beta-cell secretory capacity is still present.
Pancreas 2000 Jan
PMID:Effect of glucagon-like peptide 1(7-36)amide in insulin-treated patients with diabetes mellitus secondary to chronic pancreatitis. 1063 Mar 80

Amyloid derived from the beta-cell product islet amyloid polypeptide (IAPP) has been implicated for a beta-cell lesion in Type II diabetes mellitus. The pathogenesis of islet amyloid is poorly understood, and in addition to an amyloidogenic IAPP molecule and possibly increased concentration of IAPP, other unknown factors seem to be included. It was shown previously that polyclonal rabbit IAPP antisera label beta cells close to amyloid only weakly. Whether this lack of immunoreactivity depends on lack of IAPP or on hidden epitopes is in question. In the present study, we show that the IAPP immunoreactivity of these beta cells is possible to retrieve. On the other hand, the monoclonal IAPP antibody 4A5, which labels IAPP in beta cells, does not label IAPP in its native amyloid form. We show evidence that this lack of immunoreactivity is not dependent on conformational change of the IAPP molecules in the amyloidogenesis but is likely owing to glycation of IAPP in human islet amyloid deposits.
Pancreas 2000 Aug
PMID:Amyloid in human islets of Langerhans: immunologic evidence that islet amyloid polypeptide is modified in amyloidogenesis. 1097 16

In the GK rat model of type 2 diabetes, adenylyl cyclase (AC) expression and stimulation are increased. Whether the prevalent glucose level has any effects on AC responses is, however, unclear. We have studied concurrent insulin release and cyclic adenosine monophosphate (cAMP) generation in response to 5 microM forskolin in islets cultured for 48 hours in 5.5 or 11 mM glucose. Insulin release was impaired in GK rat islets, irrespective of culture condition, in response to 3.3 and 16.7 mM glucose and was fully restored by forskolin through exaggerated insulin responses. Stimulation of normal islets with 5 microM forskolin elicited different islet cAMP responses, which were dependent on the dose of glucose in the culture medium. Thus in normal islets cultured in 11 mM glucose, forskolin increased cAMP levels fivefold to sixfold at 3.3 and 16.7 mM glucose, whereas forskolin increased cAMP levels only twofold in islets cultured at 5.5 mM glucose. In GK islets, forskolin induced a consistently exaggerated approximately eightfold increase in cAMP generation irrespective of glucose concentration in the culture medium. In conclusion, culturing normal islets at hyperglycemic glucose levels (11 mM) primed and markedly enhanced cAMP generation in response to forskolin.
Pancreas 2001 Jan
PMID:Glucose enhances adenylyl cyclase responses in normal but not diabetic GK rat islets. 1113 73

Kidney transplantation is preferred over dialysis for management of end-stage renal disease complicating type I or type 2 diabetes, for those who are eligible. Simultaneous pancreas-kidney (SPK) or pancreas after kidney transplantation (PAK) is an important alternative to kidney transplantation alone for type I diabetes patients if the patient is able to withstand the additional risks of these procedures, because of the benefits of glucose control on other diabetic complications. Pancreas transplantation alone (PTA) is most useful for the treatment of debilitating, frequent hypoglycemia complicating type I diabetes, if renal function is adequate. One-year pancreas graft survival is best after SPK (82%) but has significantly improved after both PAK (74%) and PTA (76%). The I-year kidney graft and patient survival rates after SPK are similar to kidney transplantation alone. Pancreas transplantation normalizes glucose beyond what can be achieved with insulin therapy and has been shown to decrease progression of or improve most, if not all, diabetic end-organ complications using current immunosuppression regimens. However, the diabetologist and endocrinologist should remain involved in the care of the pancreas or kidney transplant recipient for treatment of vascular disease risk factors such as dyslipidemia, surveillance of other diabetic complications including foot ulcers, surveillance and treatment of bone loss, and management of hyperglycemia if it recurs.
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PMID:Pancreas and kidney transplantation. 1264 96

Alzheimer disease and type 2 diabetes are characterized by increased prevalence with aging, a genetic predisposition, and comparable pathological features in the islet and brain (amyloid derived from amyloid beta protein in the brain in Alzheimer disease and islet amyloid derived from islet amyloid polypeptide in the pancreas in type 2 diabetes). Evidence is growing to link precursors of amyloid deposition in the brain and pancreas with the pathogenesis of Alzheimer disease and type 2 diabetes, respectively. Given these similarities, we questioned whether there may be a common underlying mechanism predisposing to islet and cerebral amyloid. To address this, we first examined the prevalence of type 2 diabetes in a community-based controlled study, the Mayo Clinic Alzheimer Disease Patient Registry (ADPR), which follows patients with Alzheimer disease versus control subjects without Alzheimer disease. In addition to this clinical study, we performed a pathological study of autopsy cases from this same community to determine whether there is an increased prevalence of islet amyloid in patients with Alzheimer disease and increased prevalence of cerebral amyloid in patients with type 2 diabetes. Patients who were enrolled in the ADPR (Alzheimer disease n = 100, non-Alzheimer disease control subjects n = 138) were classified according to fasting glucose concentration (FPG) as nondiabetic (FPG <110 mg/dl), impaired fasting glucose (IFG, FPG 110-125 mg/dl), and type 2 diabetes (FPG >126 mg/dl). The mean slope of FPG over 10 years in each case was also compared between Alzheimer disease and non-Alzheimer disease control subjects. Pancreas and brain were examined from autopsy specimens obtained from 105 humans (first, 28 cases of Alzheimer disease disease vs. 21 non-Alzheimer disease control subjects and, second, 35 subjects with type 2 diabetes vs. 21 non-type 2 diabetes control subjects) for the presence of islet and brain amyloid. Both type 2 diabetes (35% vs. 18%; P < 0.05) and IFG (46% vs. 24%; P < 0.01) were more prevalent in Alzheimer disease versus non-Alzheimer disease control subjects, so 81% of cases of Alzheimer disease had either type 2 diabetes or IFG. The slope of increase of FPG with age over 10 years was also greater in Alzheimer disease than non-Alzheimer disease control subjects (P < 0.01). Islet amyloid was more frequent (P < 0.05) and extensive (P < 0.05) in patients with Alzheimer disease than in non-Alzheimer disease control subjects. However, diffuse and neuritic plaques were not more common in type 2 diabetes than in control subjects. In cases of type 2 diabetes when they were present, the duration of type 2 diabetes correlated with the density of diffuse (P < 0.001) and neuritic plaques (P < 0.01). In this community cohort from southeast Minnesota, type 2 diabetes and IFG are more common in patients with Alzheimer disease than in control subjects, as is the pathological hallmark of type 2 diabetes, islet amyloid. However, there was no increase in brain plaque formation in cases of type 2 diabetes, although when it was present, it correlated in extent with duration of diabetes. These data support the hypothesis that patients with Alzheimer disease are more vulnerable to type 2 diabetes and the possibility of linkage between the processes responsible for loss of brain cells and beta-cells in these diseases.
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PMID:Increased risk of type 2 diabetes in Alzheimer disease. 1474

Although there is widespread use of herbal dietary supplements that are believed to benefit type 2 diabetes mellitus, few have been proven to do so in properly designed randomized trials; their efficacy for intermediate-term glucose control remains unclear. Pancreas Tonic is a botanical mixture of traditional Indian Ayurvedic herbs currently available as a dietary supplement. We report the results of a single-center, randomized, double-blind, placebo-controlled 3-month trial of Pancreas Tonic in type 2 diabetic patients inadequately treated with diet/lifestyle or stable doses of sulfonylureas and/or metformin for at least 3 months. Patients with type 2 diabetes for >/= 1 year were entered into 2 strata of hemoglobin A(1c) (HbA(1c)) levels (stratum 1: 8.0% to 9.9%; stratum 2: 10.0% to 12.0%). All subjects began a 1-month single-blind placebo run-in phase, followed by randomization in a 2:1 ratio of active treatment: placebo, to 3 months of double-blind treatment with either Pancreas Tonic or matching placebo (2 capsules 3 times a day). Concurrent oral agents were continued unchanged throughout the study. The primary outcome was the change in HbA(1c) from randomization; results of each stratum were analyzed independently. The baseline characteristics of 36 subjects who completed the study were comparable between treatment groups. Nineteen subjects entered stratum 1 and 17 entered stratum 2. A statistically significant reduction of HbA(1c) from randomization to end-of-study was seen in the stratum 2 subjects (Pancreas Tonic: 10.1% +/- 1.0% to 8.8% +/- 1.9%, P =.004; placebo: 10.8% +/- 1.4% to 11.2% +/- 1.8%, not significant [NS]). No significant HbA(1c) reductions were seen in the stratum 1 subjects. There were no significant treatment-related differences in the fasting plasma glucose (FPG), lipids, body mass index (BMI), body composition, blood pressure, insulin sensitivity estimates using the minimal model, glucose and insulin responses to a meal challenge, quality of life, adverse events, or other safety indices between treatment groups. Pancreas Tonic was well tolerated. Treatment with Pancreas Tonic (2 capsules 3 times per day) for 3 months significantly improved glucose control in type 2 diabetic patients with HbA(1c) levels between 10.0% to 12.0%. This study represents the first properly designed, prospective intervention trial of therapy with an Ayurvedic herbal supplement for intermediate-term glucose control in type 2 diabetes.
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PMID:Effect of Pancreas Tonic (an ayurvedic herbal supplement) in type 2 diabetes mellitus. 1615 43

Several regulatory systems are implicated in the regulation of islet function and beta cell mass. Of great interest in this context are some endocrine, paracrine/autocrine, and intracrine regulators. These include, to name but a few, the gut peptides, growth factors, prostaglandins, and some vasoactive mediators such as nitric oxide, bradykinins, endothelins, and angiotensins. Apart from its potent vasoconstrictor actions, the renin-angiotensin system (RAS) that generates angiotensin II has several novel functions-stimulation and inhibition of cell proliferation; induction of apoptosis; generation of reactive oxygen species; regulation of hormone secretion; and proinflammatory and profibrogenic actions. In the pancreas, recent evidence supports the presence of an islet RAS, which is subject to activation by islet transplantation and diabetes. Such a local islet RAS, if activated, may drive islet fibrosis and reduce islet blood flow, oxygen tension, and insulin biosynthesis. Moreover, activation of an islet RAS may drive the synthesis of reactive oxygen species, cause oxidative stress-induced beta cell dysfunction and apoptosis, and thus contribute to the islet dysfunction seen in type 2 diabetes and after islet transplantation. Blockade of the RAS could contribute to the development of novel therapeutic strategies in the prevention and treatment of patients with diabetes and in islet transplantation.
Pancreas 2005 May
PMID:Pancreatic islet renin angiotensin system: its novel roles in islet function and in diabetes mellitus. 1584 Oct 36


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