UMLS:C0011860 - FACTA Search

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective impairment of glucose-induced insulin secretion and hyper-responsiveness to arginine are known features of GK rats, a genetic model of NIDDM. We focus on the ionic mechanism underlying these phenomena using patch-clamp techniques. Pancreatic islets were isolated from male GK rats and age-matched control Wistar rats and were subjected to dispersion and culture. Single channel recordings of KATP channels were performed using either on-cell mode or inside-out patch mode. Ca2+ channel currents were recorded under conventional whole-cell mode. In GK beta cells, ATP sensitivity of KATP channels itself was not altered, although glucose-induced closure of KATP channels was severely impaired. Among substrates for fuel metabolism, only dehydroxyacetone (DHA) reproduced this anomaly. On the other hand, current densities of L-type Ca2+ channels were increased in GK beta cells. Since DHA is a known substrate for glycerol phosphate shuttle, current data suggest that major metabolic deficit of GK beta cells resides in this shuttle. On the other hand, increased L-type Ca2+ channel activities might be an ionic basis for augmented insulin response to nonglucose depolarizing stimuli in GK beta cells.
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PMID:Altered functions of ion channels in diabetic beta cells. 865 42

The authors, by means of a recently introduced method, evaluated the intraplatelet concentrations of magnesium in 45 normotensive patients with type II diabetes mellitus, in 45 hypertensive diabetics and in 15 healthy controls. They also evaluated plasma and erythrocyte concentrations of the cation through direct current plasma spectrometer. Both normotensive and hypertensive diabetics showed a reduction in plasma, erythrocyte, and platelet concentrations of magnesium compared to controls. On the contrary, no significant difference was found between hypertensive and normotensive diabetics with regard to plasma and erythrocyte magnesium, whereas intraplatelet assay of the ion pointed out significantly lower concentrations of magnesium in hypertensive compared to normotensive patients (56.4 +/- 9.0 vs 60.7 +/- 10.2 micrograms/10(8) cells--p < 0.05). The authors believe that intraplatelet assay of magnesium may be the most reliable method for the evaluation of the cation in hypertensive diabetics, probably because platelets share common features with smooth muscle cells, including the alpha-2-adrenoceptor cyclase system and a coupling mechanism concerning the calcium-dependent contraction.
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PMID:Magnesium levels in plasma, erythrocyte, and platelet in hypertensive and normotensive patients with type II diabetes mellitus. 883 76

Intracellular calcium ([(Ca2+)i]) plays a role in many cellular functions, and is involved in the pathogenesis of some conditions observed in non-insulin dependent diabetic patients (NIDDM), such as hypertension and insulin resistance. Hyperinsulinemia and hyperglycemia are also implicated in the pathogenesis of chronic diabetes complications. It is not clear whether disturbances in [(Ca2+)i] are accounted for only by metabolic abnormalities of diabetes or by other mechanisms. The aim of this study was to investigate [(Ca2+)i] handling by skin fibroblasts in NIDDM patients with similar features regarding diabetes duration and metabolic control, but who differ concerning blood pressure levels and albumin excretion rate. Using a fluorimetric technique with the indicator Fura-2/ AM, we investigated the effect of chronic exposure to insulin and glucose on [(Ca2+)i] after FGF stimulation in fibroblasts from NIDDM with hypertension alone (NIDDM H+M-) and with hypertension and microalbuminuria (NIDDM H+M+) in comparison with normotensive normoalbuminuric NIDDM (NIDDM H-M-) and control subjects (C). We studied also a group of hypertensive non-diabetic subjects (HYPER). We found that (1) FGF increases [(Ca2+)i] in all subjects; (2) insulin or high glucose per se increase [(Ca2+)i] in NIDDM H+M+ and NIDDM H+M- with respect to NIDDM H-M- and C; (3) HYPER show a [(Ca2+)i] response similar to that of NIDDM H+M- and NIDDM H+M+; (4) when stimuli are combined, all NIDDM have altered [(Ca2+)i] with respect to C, but NIDDM H+M-, NIDDM H+M+ and HYPER have higher values than NIDDM H-M-. This disorder in [(Ca2+)i] appears to be an intrinsic feature of a subgroup of hypertensive NIDDM patients, which persists in cultured cells, at least partially independent of the metabolic challenge of diabetes in vivo, and could contribute to the development of their renal and cardiovascular complications.
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PMID:Intracellular calcium handling by fibroblasts from non-insulin dependent diabetic patients with and without hypertension and microalbuminuria. 884 Feb 94

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

The open trial was designed to evaluate the effects of long-term antihypertensive treatment with the calcium-channel blocker, manidipine and the angiotensin converting enzyme (ACE) inhibitor, delapril on insulin sensitivity in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients with essential hypertension. We measured the insulin sensitivity index (SI) and the glucose-effectiveness (SG) by the use of Bergman's minimal model method in 18 hypertensive NIDDM patients before and after administration of manidipine (group A) or delapril (group B) for 3 months. Manidipine treatment for 3 months significantly improved SI in group A from 3.35 +/- 0.61 (x 10(-4) min-1 microU-1 ml-1) to 4.70 +/- 1.34 (P < 0.05). Delapril treatment for 3 months also significantly improved SI in group B from 3.56 +/- 1.04 to 5.00 +/- 0.87 (P < 0.05). Manidipine significantly improved SG in group A from 1.60 +/- 0.64 (x 10(-2) min) to 2.19 +/- 0.38 (P < 0.05). Delapril treatment also significantly improved SG in the group B from 1.41 +/- 0.56 to 1.91 +/- 0.35 (P < 0.05). Manidipine and delapril did not affect urinary C-peptide excretion for 24 h in the hypertensive NIDDM patients. Treatment with manidipine or delapril significantly reduced systolic and diastolic blood pressures in the hypertensive NIDDM patients. There were no differences between plasma glucose, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions, heart rate and body weight after 3 months on manidipine or delapril. This study confirmed the improving effects on SI and SG by long-term treatment with manidipine or delapril in the hypertensive NIDDM patients.
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PMID:Effect of manidipine and delapril on insulin sensitivity in type 2 diabetic patients with essential hypertension. 887 75

The aim of our study was to compare the effect of captopril--the angiotensin-converting enzyme inhibitor, nifedipine--the calcium antagonist, and prazosin--the alpha blocker, on the secretory function of pancreatic beta-cells in hypertensive patients with NIDDM and with normal glucose tolerance. The effect of a 2-week treatment with nifedipine, captopril and prazosin upon glycaemia, serum insulin (IRI) and C-peptide (CP) following oral and intravenous glucose load were investigated in three groups, each including 10 non-diabetic patients with essential hypertension (h) and 10 hypertensive type 2 (non-insulin-dependent) diabetics (h + d), aged 32-63 years. Nifedipine produced increase in glycaemia in the oral test in both groups. In the (h) group, but not in the (h + d) group, the drug caused reduction of the glucose-dependent increases in serum IRI and CP, more marked with respect to CP, as expressed by the decrease in the molar serum CP/IRI ratio. These results indicate that in non-diabetic patients, nifedipine reduces the early response of beta-cells to glucose, but this effect is partly compensated by a decreased insulin uptake by the liver. In patients with type 2 diabetes, this phenomenon does not become manifest because of absence or reduction in the early glucose-dependent insulin release. After captopril, lower values of glycaemia and serum IRI and CP were observed in both groups suggesting an improvement of insulin sensitivity. In conclusion, nifedipine has a small influence, and captopril and prazosin are devoided of any influence on the secretory function of pancreatic beta-cells. These drugs may be recommended for the treatment of hypertension in patients with type 2 (non-insulin-dependent) diabetes.
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PMID:Effect of nifedipine, captopril and prazosin on secretory function of pancreatic beta-cells in hypertensive patients with type-2 (non-insulin-dependent) diabetes and in hypertensive non-diabetics. 887 77

Nutrition and food science have each enhanced the development of an abundant, nutritious, safe food supply. A healthy diet should contain all of the required nutrients and sufficient calories to balance energy expenditure and provide for growth and maintenance throughout the life cycle. Importantly, dietary factors are associated with 5 of the 10 leading causes of death, including coronary heart disease, certain types of cancer, stroke, noninsulin dependent diabetes mellitus and atherosclerosis. National health care expenditures for 1990 totaled $666 billion of which 30% are related to inappropriate diet. Identification of external factors that contribute to premature death would aid preventive efforts, improve the quality of life, and reduce health care costs. Even though genetic predisposition increases susceptible people's risk for many of these chronic diseases, these conditions may be diminished or prevented by improvements in the American diet. Each stage of the life cycle has specific nutrient needs. Throughout infancy, childhood and adolescence nutrients are required to meet the growth processes as well as cognitive function. During pregnancy nutrients are required for both mother and developing infant needs. Adult nutrition focuses on tissue maintenance, nutrient and energy needs, and disease prevention. As the population of elderly increase in number and greater age, nutritional needs must be met to minimize certain disease states and assure the quality of life. Nutrition associated health risks have been identified for coronary heart disease, cancer and diabetes mellitus. Recommendations for each includes a decrease in dietary fat, awareness of caloric intake and enhancement of nutrient density including an increase in fruit and vegetables. These recommendations also impact obesity and diminish the compounding of other disease states affected by excessive body weight. Calcium intake at early ages affects development of bone density and manifestation of osteoporosis. Current gaps in knowledge are also identified that could improve health. Numerous nutrients are being examined for their regulation of specific gene expressions and in the processes of transcription and translation. To offer food products with greater nutrient density or improved functional health ingredients, modification of existing foods is needed to assure an improved diet. Policies to improve health require integration of nutrition needs with economic growth and development, agriculture and food production, processing, marketing, health care and education, and includes changing life styles and food choices. Increased research support is required to achieve national health goals with emphasis on nutrition and food sciences. Education methods must be improved to better inform consumers, to encourage food producers and manufactures to produce healthier foods, to assure training of future professionals and to provide legislators with the basis to make informed decisions. Recommendations to CFERR are identified. Improved quality and availability of nutritious foods will result in a healthier, more productive population. A decrease in the occurrence and duration of chronic disease should diminish the cost of health care and allow these resources to further benefit the nation. International concerns about undernutrition include 780 million people who are malnourished, lacking sufficient food to meet their basic nutritional needs for protein and energy, and 2 billion people who subsist on diets lacking essential nutrients needed for growth, development and physiological maintenance. National concerns about undernutrition exist based on incomplete data identified by indices of hunger and characterized by an increased demand for food assistance for women, children and the elderly. Major health problems in the US impacted by diet and nutrition include coronary heart disease, atherosclerosis, some types of cancer, non-insulin dependent diabetes mellitus, hypert
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PMID:Interrelationships of food, nutrition, diet and health: the National Association of State Universities and Land Grant Colleges White Paper. 889 67

Glucose-dependent sequestration of Ca2+ into endoplasmic reticulum and its subsequent release play an important role in the control of intracellular Ca2+ concentration, which regulates insulin secretion in pancreatic beta-cells. The active uptake of cytosolic Ca2+ into endoplasmic reticulum is mediated by sarco-(endo)plasmic reticulum Ca(2+)-ATPases (SERCAs). We found, using RT-PCR with isoform-specific primers, that SERCA 2 and SERCA 3 mRNAs are co-expressed in human and rat islets of Langerhans and in the RINm5F beta-cell line. Immunochemical analysis also revealed the existence of two SERCA proteins with molecular masses of 110 and 115 kDa in beta-cell membranes. The 115 kDa protein was identified as SERCA 2b by its reaction with an isoform-specific antibody and the 110 kDa protein most probably corresponds to SERCA 3. The presence of two functionally different SERCA isoforms raises the possibility that they are located in distinct Ca2+ stores. There is evidence that altered Ca2+ handling in the beta-cell may contribute to the decreased insulin secretion seen in non-insulin dependent diabetes mellitus (NIDDM). We therefore investigated SERCA 2 and SERCA 3 mRNA expression by quantitative RT-PCR in islets prepared from Goto-Kakizaki (GK) rats, a non-obese spontaneous model of NIDDM. We found a significant reduction (about 68%) in SERCA 3 isoform expression. Since SERCA 2 expression was not significantly reduced, these genes are independently regulated and probably play distinct roles in islets of Langerhans. The marked decrease of SERCA 3 expression may constitute a defect in Ca2+ signalling in GK rat islets which could be a component of NIDDM.
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PMID:Isoforms of endoplasmic reticulum Ca(2+)-ATPase are differentially expressed in normal and diabetic islets of Langerhans. 891 90

Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria. Calcium channel blockers (CCBs) have variable effects on proteinuria; their long-term effects on progression of diabetic nephropathy are not known. The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus (NIDDM) by a degree comparable to ACE inhibitors, given similar levels of blood pressure control. To test this hypothesis we randomized 52 patients with NIDDM associated nephropathy and hypertension, mean age of 63 +/- 8 years, to either the ACE inhibitor, lisinopril (N = 18), nondihydropyridine CCBs (NDCCBs), verapamil SR (N = 8) or diltiazem SR (N = 10), or the beta blocker, atenolol (N = 16). Goal blood pressure was < or = 140/90 mm Hg. Patients were followed for a mean period of 63 +/- 7 months. The primary end point was change in creatinine clearance (CCr) slope in each group. There was no significant difference in mean arterial pressure reduction among the groups over the study period (P = 0.14). The mean rate of decline in CCr was greatest in the atenolol group (-3.48 ml/min/year/1.73 m2; P < 0.0001). There was no difference in the CCr slopes between lisinopril and NDCCBs groups (P = 0.36). Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups (P > 0.99). Therefore, in persons with renal insufficiency secondary to NIDDM, similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol. Moreover, this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria, findings not observed in the atenolol group.
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PMID:Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. 891 31

This study aimed to investigate the relationship between microalbuminuria and office blood pressure (BP) as compared with ambulatory BP in patients with diabetes mellitus under everyday practice conditions. It was also undertaken to assess the effect of the angiotensin converting enzyme inhibitor cilazapril on diabetes-associated albuminuria. Ambulatory BP was recorded during daytime in 54 patients with type II diabetes mellitus at the end of a 4-week period during which they received no vasoactive drug. The difference between office and ambulatory BP was unpredictable in the individual patient. There was no significant correlation between either ambulatory or office BP and urinary albumin/p5eatinine ratio. Fifty-one patients underwent a 40-week treatment with 5 mg/day of cilazapril. There was, in the absence of satisfactory BP control, the possibility of adding the calcium antagonist amlodipine (5 mg/day) from the 10th week onward and 12.5 mg/day of hydrochlorothiazide from the 20th week onward. Office mean BP was significantly reduced after 30 to 40 weeks of therapy in patients with normoalbuminuria (n = 19, -14%, P < .001), in those with microalbuminuria (n = 22, -6.6%, P < .01), as well as in those with clinical proteinuria (n = 9, -11.4%, P < .01). During the same time, the urinary albumin/creatinine ratio was not modified in normoalbuminuric patients (n = 19, +24.6%, P = .72) as well as in those with clinical proteinuria (n = 9, -29.4%, P = .09). On the other hand this value was significantly reduced for the group with microalbuminuria (n = 23, -24.3%, P < .05). In the overall population, as well as in hyperalbuminuric patients (patients with microalbuminuria + patients with clinical proteinuria), the reduction of the albumin/ creatinine ratio was also significant (n = 51, -7%, P < .01 and n = 32, -25,7%, P < .01, respectively). In conclusion, the findings of this study performed by practicing physicians show that ambulatory BP may differ greatly from office BP in diabetic patients. They also indicate that urinary albumin excretion is poorly correlated with office and ambulatory BP in type II diabetics. Finally, they demonstrate the antiproteinuric action of prolonged treatment with the angiotensin converting enzyme inhibitor cilazapril, whether given alone or combined with amlodipine.
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PMID:Albuminuria in diabetes mellitus: relation to ambulatory versus office blood pressure and effects of cilazapril. 897 94

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