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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.
Diabetes 1976 Mar
PMID:Effect of streptozotocin on red-blood-cell-reduced glutathione: modification by glucose, nicotinamide, and epinephrine. 13 Feb 72

The uptake of the nicotinamide adenine dinucleotide (NAD)-precursors nicotinamide, nicotinic acid and tryptophan in the pancreatic islets of mice was studied by use of autoradiographic methods. The ability of these substances to prevent streptoxotocin diabetes was studied in the same species. It was found that only nicotinamide was strongly accumulated in the pancreatic islets and nicotinamide was also the only NAD-precursor which protected against the streptoxotocin diabetes. Apparently there is a relationship between the ability of the NAD-precursors to be taken up in the pancreatic islets and their ability to prevent streptoxotocin diabetes.
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PMID:The uptake in the pancreatic islets of nicotinamide, nicotinic acid and tryptophan and their ability to prevent streptozotocin diabetes in mice. 13 65

A literature review of the effect of oral contraceptive (o.c.) use on various metabolic processes is presented. Several studies show an adverse effect of o.c. use on subclinical diabetes and on patients with manifest insulin-independent diabetes. Some researchers have found a beneficial effect of o.c. use on older diabetics. It has not been determined whether the estrogen or gestagen component of o.c.s is responsible for this decrease in glucose tolerance, nor has the mechanism for this effect been discovered. Changes in various plasma protein concentrations have been observed during o.c. use, which affect the blood coagulation and the blood pressure regulation systems. The estrogen component appears to be responsible for the increase in the serum triglyceride concentration during o.c. use; the mechanism is still unknown. Some studies indicate that o.c. use causes an increase in serum cholesterol levels, which could promote gall stone formation. An increase in Vitamin A concentration has been observed during o.c. use. Riboflavin, folic acid, vitamin B 12, and ascorbic acid levels have been shown to decrease during o.c. use. A decrease in pyridoxin levels during o.c. use indicates an increased metabolism of tryptophan to nicotinic acid robosyl-5-phosphate. This would cause a decrease in serotonin production, which could be a cause of the depression experienced by some o.c. users. An increase in the plasma copper and caeruloplasmin levels during o.c. use is apparently due to the estrogen component. An increase in transferrin and the serum iron levels have been observed during o.c. use. Contradictory findings are reported concerning the plasma concentration of zinc.
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PMID:[Metabolic studies under administration of oral contraceptives. A review]. 34 1

Pancreatectomized dogs developed hypertriglyceridemia. This probably resulted from a lack of insulin rather than a lack of glucagon, as it did not develop either in pancreatectomized dogs maintained on insulin, or in dogs with all but the uncinate process of the pancreas removed. The increase in plasma triglycerides was preceded by a decrease in post-heparin lipolytic activity (PHLA) and an increase in FFA. As the hypertriglyceridemia developed in fasted dogs who had previously been on fat-free diets, the triglyceride fatty acids (TGFA) were nondietary. These endogenous TGFA originated from adipose tissue rather than from de novo synthesis. The composition of the lipoprotein TGFA was identical to that of adipose tissue. Furthermore, nicotinic acid blocked the FFA increase and the development of the hypertriglyceridemia. However, it did not prevent the fall of PHLA. Although their TGFA were entirely nondietary, the lipoproteins in these diabetic dogs resembled chylomicrons in their electrophoretic mobility, size, density, and composition. Surgical, histological and tracer studies suggested that in addition to the liver, the intestinal mucosa makes these lipoproteins. The tracer studies also suggested that circulating FFA might enter the intestinal mucosal cells directly and be esterified.
Diabetes 1975 Mar
PMID:Production of chylomicron-like lipoproteins from endogenous lipid by the intestine and liver of diabetic dogs. 111 49

Investigations were initiated to examine the rate of imbalances in carnitine metabolism in the pathogenesis of diabetic vascular changes in the retina, peripheral nerves, aorta and kidney. It appears that glucose/diabetes-induced vascular dysfunction and early vascular structural changes are mediated by hyperglycaemic hypoxia i.e. glucose-induced metabolic imbalances that cause an increase in the reduced nicotinamide-adenine dinucleotide/nicotinic acid dehydrogenase ratio, and are linked to imbalances in carnitine metabolism.
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PMID:The roles of glucose-induced metabolic hypoxia and imbalances in carnitine metabolism in mediating diabetes-induced vascular dysfunction. 130 5

NEFAs characteristically are elevated in obese NIDDM patients in both the basal state and after insulin. This elevation might aggravate glycemic control both by decreasing peripheral glucose disposal (glucose-fatty acid cycle), and by increasing HGO. Thus, lowering plasma NEFA levels might improve carbohydrate metabolism. We therefore measured HGO and fuel use (by indirect calorimetry) both in the basal state and during the last 30 min of a hyperinsulinemic clamp (0.025U.kg-1.h-1) in 8 obese NIDDM patients (BMI 34.8 +/- 1.0 kg/m2) after complete overnight suppression of plasma NEFA levels with acipimox, a new nicotinic acid analogue. After acipimox, mean basal plasma NEFA and glycerol levels were lower than control values (0.11 +/- 0.02 vs. 0.65 +/- 0.04 mM, P < 0.001; and 16 +/- 3 vs. 68 +/- 7 microM, P = 0.004, respectively) and were accompanied by a fall in lipid oxidation (acipimox vs. placebo: 16.1 +/- 1.2 vs. 38.8 +/- 2.4 mg.m-2 x min-1; P < 0.001) and a rise in glucose oxidation (91.1 +/- 6.2 vs. 54.1 +/- 9.0 mg.m-2 x min-1; P = 0.002). Basal HGO and fasting plasma glucose levels were lower (94.1 +/- 9.2 vs. 118.5 +/- 9.5 mg.m-2 x min-1, P = 0.01; and 8.3 +/- 1.2 vs. 9.8 +/- 1.2 mM; P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Nov
PMID:Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects. 139 16

Patients with diabetes mellitus are at increased risk of morbidity and mortality from macrovascular disease manifesting as coronary heart disease, cerebrovascular accidents, and peripheral vascular disease. Increased frequency of dyslipidemia, hyperglycemia, obesity, hypertension, and associated nephropathy may contribute to accelerated atherogenesis in diabetic patients. Therefore, besides intensive control of hyperglycemia, management of dyslipidemia, hypertension, and obesity should also be emphasized in diabetic patients. Those who smoke should be strongly encouraged to quit smoking. Besides attempts to achieve normal levels of plasma lipoproteins, consideration also should be given to normalization of compositional abnormalities of various lipoproteins in patients with diabetes mellitus. The therapeutic goals for cholesterol reduction should be lower in diabetic patients than nondiabetic subjects. The first step is to achieve good metabolic control of diabetes mellitus by diet, exercise, and weight reduction and, if needed, with sulfonylureas or insulin therapy. Because most of the patients with insulin-dependent diabetes mellitus achieve normal levels of plasma lipoproteins with intensive insulin therapy, lipid-lowering medications are rarely needed. In patients with non-insulin-dependent diabetes mellitus, however, dyslipidemia often persists despite good glycemic control. Lipid-lowering medications should be considered in such patients. Because nicotinic acid can cause marked deterioration in glycemic control, and bile acid-binding resins may accentuate hypertriglyceridemia, these agents are less desirable for use by diabetic patients. Inhibitors of hydroxymethylglutaryl coenzyme A reductase may be preferred in patients with elevated LDL cholesterol and mld hypertriglyceridemia. For diabetic patients with marked hypertriglyceridemia, however, fibric acid derivatives should be the drug of choice.
Diabetes 1992 Oct
PMID:Lipid-lowering therapy and macrovascular disease in diabetes mellitus. 152 29

There are elevated fatty acid levels in non-insulin-dependent diabetes mellitus that are due to diminished insulin action in inhibiting fatty acid release from adipocytes. Insulin therapy and other inhibitors of fatty acid release from adipocytes (e.g., nicotinic acid) suppress these elevated fatty acid levels and bring about a reduction in hyperglycemia. One mechanism by which fatty acids may be causal in hyperglycemia is in stimulating gluconeogenesis in the liver in the postabsorptive state. Another mechanism is in attenuating glucose disposal in skeletal muscle in the fed state. Potential nonglycemia-related effects of fatty acids are in substrate utilization in the heart and lipid synthesis in the liver. Inhibition of fatty acid oxidation is useful in reducing hyperglycemia by inhibiting glucose production in humans. However, there is less evidence that such inhibition can be useful in increasing glucose utilization in muscle, as predicted by the Randle hypothesis. This, coupled with potential adverse effects on heart muscle, make liver targeting of fatty acid oxidation inhibitors an important factor in their potential for development. Although such agents have advantageous effects on lipid metabolism, overdosing can lead to adverse liver lipid effects via the same mechanism. These adverse liver lipid effects could be minimized by development of reversible inhibitors that allow fatty acid oxidation to occur only during the overnight fast. The potential usefulness of such agents is evident; however, no drug that meets these objectives has been developed.
Diabetes Care 1992 Jun
PMID:Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. 160 Aug 36

An elevated plasma proinsulin (PI) to immunoreactive insulin (IRI) ratio occurs in relatives of patients with insulin-dependent diabetes mellitus and in subjects with non-insulin-dependent diabetes mellitus. To determine whether this alteration is the result of B-cell dysfunction and/or insulin resistance, we infused nicotinic acid for 3 weeks to produce insulin resistance in five adolescent male baboons before and after the administration of streptozocin (200 mg/kg). We measured basal PI and IRI levels and the acute incremental PI (APIR) and IRI (AIRIR) responses to iv arginine. The quantity of IRI comprised of PI was calculated in the basal state (PI/IRI) and following arginine injection (APIR/AIRIR). Streptozocin administration did not change the fasting plasma glucose (FPG) compared to that in the normal animals (4.7 +/- 0.3 vs. 4.3 +/- 0.2 mM) but raised the PI/IRI (16.4 +/- 3.4 vs. 5.9 +/- 1.7%) and APIR/AIRIR (7.1 +/- 1.0 vs. 2.8 +/- 1.0%) due to a concurrent reduction in IRI and increase in PI concentrations. The induction of experimental insulin resistance with nicotinic acid in the normal animals had no effect on the FPG (4.4 +/- 0.2 mM) but in the streptozocin treated animals, fasting hyperglycemia (8.3 +/- 1.7 mM) developed. Neither the basal PI/IRI (10.2 +/- 2.2%) or the APIR/AIRIR (2.3 +/- 0.6%) increased in the insulin-resistant streptozocin animals thus being no different to that of normal control animals before or during experimental insulin resistance. We conclude that disproportionate proinsulinemia is a manifestation of B-cell damage from streptozocin which is not exacerbated by insulin resistance or hyperglycemia.
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PMID:Effect of insulin resistance and hyperglycemia on proinsulin release in a primate model of diabetes mellitus. 172 20

Cardiovascular disease, and in particular ischemic heart disease, is the principal cause of morbidity, functional disability, and mortality in patients with non-insulin-dependent (type II) diabetes. The main risk factors for the macrovascular complications of diabetes are dyslipidemia, hypertension, and cigarette smoking. Although degree of hyperglycemia is a risk factor for microvascular complications, it is not a prominent risk factor for macrovascular complications. Nevertheless, there are theoretical reasons for believing that glycemic control could lower cardiovascular risk. For example, glycemic control may both improve clearance and suppress hepatic overproduction of very-low-density lipoprotein. Moreover, there is direct empirical evidence that improved glycemic control can favorably alter lipid profiles in type II diabetic patients. Despite this, the only clinical trial that has assessed cardiovascular mortality as an end point in diabetic subjects (i.e., the University Group Diabetes Program) failed to demonstrate a benefit of glycemic control. In this study, the insulin-variable group, which achieved sustained glycemic control relative to the placebo group, had essentially the same cardiovascular mortality as the latter group. All of the conventional lipid-lowering agents have been shown to produce favorable changes in lipid profiles in diabetic subjects. However, the optimum regimen remains to be defined. Metabolic differences between diabetic and nondiabetic subjects mean that the optimum lipid-lowering regimens for the two categories of patients may differ. For example, nicotinic acid, which is a powerful lipid-altering drug, may worsen glucose intolerance. The characteristic lipid abnormalities in type II diabetic subjects are hypertriglyceridemia and low high-density lipoprotein cholesterol, not hypercholesterolemia. Although the role of hypertriglyceridemia as a cardiovascular risk factor in the general population has been questioned, there is evidence that this lipid abnormality may play a stronger role in diabetic subjects. For all of the above reasons, there is an urgent need for large-scale clinical trials assessing cardiovascular end points and testing various strategies of improving lipid profiles in diabetic subjects, particularly given the fact that all of the current generation of lipid-lowering trials have systematically excluded diabetic patients.
Diabetes Care 1991 Dec
PMID:Dyslipidemia in type II diabetes. Implications for therapeutic intervention. 177 1


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