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

Adult rats, that had been injected with streptozotocin during the neonatal period, received a primed constant infusion of succinic acid dimethyl ester (SAD; 0.5 micromol followed by 0.25 micromol x min(-1), both per g body wt.) in saline for 15 min and, at the 5th min of such an infusion, an intravenous injection of GLP-1 (5 pmol per g body wt.). Within 2 min, the ester increased the plasma insulin concentration by 0.33+/-0.05 nM. Likewise, within 2 min, GLP-1 provoked a marked increase in plasma insulin concentration; such an increase was comparable in rats infused with either saline or SAD, with an overall mean value of 0.93+/-0.07 nM. In the rats infused with SAD, however, the secretory response to GLP-1 appeared more sustained than in the saline-infused animals. For instance, the paired ratio for the insulinogenic index at 10/2 min after GLP-1 injection averaged 30.5+/-4.0% in SAD-infused rats, as compared (P<0.025) to only 17.0+/-2.5% in saline-infused animals. These findings suggest that succinic acid esters could be used to prolong the insulinotropic action of GLP-1 in the treatment of type-2 diabetes.
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PMID:Prolongation of the insulinotropic action of glucagon-like peptide 1 by the dimethyl ester of succinic acid in an animal model of type-2 diabetes. 1093 97

The insulinotropic action of GLP-1 is modulated by the nutritional environment of islet B-cells. This study explores whether an ester of succinic acid could be used to potentiate the insulin secretory response to GLP-1 in vivo. Fed anaesthetized male rats received a primed constant infusion (0.5 micromol followed by 0.25 micromol x min(-1) both per g body wt) of succinic acid dimethyl ester (SAD) in saline for 15 min and, at the 5th min of such an infusion, an intravenous injection of GLP-1 (5 pmol/g body wt). The ester provoked a rapid, sustained and reversible increase in plasma insulin concentration. In the SAD-infused rats, the increment in plasma insulin concentration caused by GLP-1 was more pronounced and more sustained than in saline-infused rats. It is proposed, therefore, that suitable succinic acid esters could be used to potentiate the insulinotropic action of GLP-1 in Type II (non-insulin-dependent) diabetes.
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PMID:Potentiation of the insulinotropic action of GLP-1 by succinic acid dimethyl ester in fed anaesthetized rats. 1098 25

In a case control study, we assessed the prevalence of bacterial urinary tract infections (UTI) and renal scarring in 155 consecutive type 1 (n=102) and type 2 (n=53) diabetic individuals and 128 healthy controls. Subjects who received antibiotics during the past 6 months, pregnant women and those with overt renal failure were excluded. In all subjects, urine culture and 99m Technetium (Tc) dimercapto-succinic acid renal scan was performed. UTI was diagnosed if two consecutive urine cultures grew the same organism with at least 10(5) colony forming unit (cfu)/ml in asymptomatic and at least 10(4) cfu/ml in symptomatic subjects, respectively. Renal scan was considered abnormal if focal or multiple tracer uptake defects and/or break in cortical outline were observed. The prevalence of UTI in diabetes mellitus was higher, when compared to that in controls (9% vs. 0.78%, P=0.005). Escherichia coli was the most commonly grown organism (64.3%), followed by Staphyloccocus aureus (21.4%) and Klebsiella pneumoniae (14.3%). Prevalence of renal scarring was higher in patients with diabetes (28/155, 18.0%), when compared to that of controls (7/128, 5.4%, P=0.002). Fifty percent of patients with diabetes and UTI had renal scarring. The prevalence in diabetics with no UTI was also higher, when compared to controls (14.8 vs. 5.5%, P<0.01). The prevalence of UTI as well as renal scarring was significantly higher in females, when compared to male diabetics. No significant difference in vascular events, hypertension, proteinuria, renal function tests and HbA1 was observed in patients with and without renal scar. Thus, patients with diabetes mellitus have 10- and 3-folds increased risk of UTI and renal scarring, respectively. The results could help prioritize protocols for management of UTI among patients with diabetes mellitus.
Diabetes Res Clin Pract 2001 Sep
PMID:Prevalence of urinary tract infection and renal scars in patients with diabetes mellitus. 1148 34

It was recently proposed that suitable succinic acid esters could be used to potentiate the insulinotropic action of glucagon-like peptide 1 (GLP-1) in the treatment of type-2 diabetes mellitus. In such a perspective, the present study aimed mainly at investigating whether exendin-4 (Ex-4), a peptide structurally related to GLP-1(7-36)amide, and succinic acid dimethyl ester (SAD) also act synergistically upon insulin secretion in anaesthetized rats. Despite a higher plasma insulin concentration in SAD-infused rats (5.5+/-1.1 ng/ml) than in saline-infused animals (1.9+/-0.7 ng/ml), the intravenous injection of Ex-4 augmented to a greater extent the plasma concentration of insulin in the former rats (+7.4+/-2.5 ng/ml) than in the latter animals (+2.8+/-0.6 ng/ml). These findings document that the insulinotropic actions of Ex-4 and GLP-1 display comparable nutrient dependency, being both potentiated by a non-glucidic nutrient secretagogue such as SAD.
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PMID:Synergistic insulinotropic effects of succinic acid dimethyl ester and exendin-4 in anaesthetized rats. 1149 54

The effect of phensuccinal, a low-toxic succinic acid derivative, on the function of pancreatic beta-cells in the evolution of absolute insulin insufficiency was studied in rats with neonatally induced streptozotocin diabetes mellitus. Phensuccinal (25 mg/kg body weight) prevented disorders in the secretory response of beta-cells to glucose load at all stages of the study (2, 5, and 14 days after diabetes induction). This effect was realized via stimulation of the regenerative processes in the insulin-producing system of the pancreas and activation of the antioxidant system in diabetic animals.
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PMID:Effect of phensuccinal on pancreatic beta-cells in rats with neonatally induced streptozotocin diabetes mellitus. 1168 46

To investigate the influence of the succinic acid treatment on geriatric patients with type 2 diabetes. Succinic Acid has some positive biological properties. One of its is a neglecting of an aerobic glycolysis. In this study we evaluated the efficacy of the combination of the succinic acid ("MITOMIN") on treating of diabetic neuropathy of geriatric patients with type 2 diabetes. The analysis was carried out using 26 patients (aged 60-76 years). The duration of diabetes was 9.15 +/- 1.43 years. Biomedical parameters were measured by standard methods; microalbuminuria was measured by "Micral-Test". Quality of life (psychosocial disorders) was estimated with the help of "SANDOZ"-scale for geriatric assessment. The therapy was assigned 1.5 g of mitomin per day during a month. All patients were examined on having late diabetic complications: 7.69%--had diabetic retinopathy; 11.54%--diabetic nephropathy; 73.08%--diabetic neuropathy; 46.15%--chronic failure of brain vessels; 11.5%--macroangiopathy of lower extremities and 100%--had ischeamic heart disease of different levels. Mitomin therapy improved basal and postprandial glycemic control (NS), variance of pallesthesia (p < 0.001), parameters of quality of life, i.e. depression (p < 0.001), anxiety (p < 0.01), short memory (p < 0.05) and emotionality (p < 0.001). Mitomin therapy plays a positive role in management of elderly patients with type 2 diabetes. It improves glycemic control, pallestesia and quality of life. Combination of succinic acid renders central and peripheral neuropathy protective efficacy.
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PMID:[Diabetes mellitus in the elderly: succinic acid compounds in treating diabetic neuropathies]. 1209 44

The secondary signals emanating from increased glucose metabolism, which lead to specific increases in proinsulin biosynthesis translation, remain elusive. It is known that signals for glucose-stimulated insulin secretion and proinsulin biosynthesis diverge downstream of glycolysis. Consequently, the mitochondrial products ATP, Krebs cycle intermediates, glutamate, and acetoacetate were investigated as candidate stimulus-coupling signals specific for glucose-induced proinsulin biosynthesis in rat islets. Decreasing ATP levels by oxidative phosphorylation inhibitors showed comparable effects on proinsulin biosynthesis and total protein synthesis. Although it is a cofactor, ATP is unlikely to be a metabolic stimulus-coupling signal specific for glucose-induced proinsulin biosynthesis. Neither glutamic acid methyl ester nor acetoacetic acid methyl ester showed a specific effect on glucose-stimulated proinsulin biosynthesis. Interestingly, among Krebs cycle intermediates, only succinic acid monomethyl ester specifically stimulated proinsulin biosynthesis. Malonic acid methyl ester, an inhibitor of succinate dehydrogenase, also specifically increased glucose-induced proinsulin biosynthesis without affecting islet ATP levels or insulin secretion. Glucose caused a 40% increase in islet intracellular succinate levels, but malonic acid methyl ester showed no further effect, probably due to efficient conversion of succinate to succinyl-CoA. In this regard, a GTP-dependent succinyl-CoA synthetase activity was found in cytosolic fractions of pancreatic islets. Thus, succinate and/or succinyl-CoA appear to be preferential metabolic stimulus-coupling factors for glucose-induced proinsulin biosynthesis translation.
Diabetes 2002 Aug
PMID:Succinate is a preferential metabolic stimulus-coupling signal for glucose-induced proinsulin biosynthesis translation. 1214 63

Esters of succinic acid are potent insulin secretagogues, and have been proposed as novel antidiabetic agents for type 2 diabetes. This study examines the effects of acute and chronic exposure to succinic acid monomethyl ester (SAM) on insulin secretion, glucose metabolism and pancreatic beta cell function using the BRIN-BD11 cell line. SAM stimulated insulin release in a dose-dependent manner at both non-stimulatory (1.1 mM) and stimulatory (16.7 mM) glucose. The depolarizing actions of arginine also stimulated a significant increase in SAM-induced insulin release but 2-ketoisocaproic acid (KIC) inhibited SAM induced insulin secretion indicating a possible competition between the preferential oxidative metabolism of these two agents. Prolonged (18 hour) exposure to SAM revealed decreases in the insulin-secretory responses to glucose, KIC, glyceraldehyde and alanine. Furthermore, SAM diminished the effects of non-metabolized secretagogues arginine and 3-isobutyl-1-methylxanthine (IBMX). While the ability of BRIN-BD11 cells to oxidise glucose was unaffected by SAM culture, glucose utilization was substantially reduced. Collectively, these data suggest that while SAM may enhance the secretory potential of non-metabolized secretagogues, it may also serve as a preferential metabolic fuel in preference to other important physiological nutrients and compromise pancreatic beta cell function following prolonged exposure.
Int J Exp Diabetes Res 2001
PMID:Differential acute and long term actions of succinic acid monomethyl ester exposure on insulin-secreting BRIN-BD11 cells. 1236 22

Glucagon-like peptide-1 (GLP-1), an incretin hormone which helps to regulate plasma glucose levels, is considered a potential agent for the treatment of type-2 diabetes mellitus, because of its insulinotropic capacity and insulinomimetic actions. In normal conditions, the beta-cell secretory response to GLP-1 is modulated by the extracellular concentration of D-glucose; however, the recognition of D-glucose by the beta-cell is often impaired in type-2 diabetes, and this could impede the full GLP-1 insulinotropic action. Non-glucidic substrates, such as the dimethyl ester of succinic acid, restore the effect of GLP-1 in the isolated perfused rat pancreas of normal or diabetic rats, in the absence of any other exogenous nutrient; likewise, the dimethyl ester of succinic or L-glutamic acid, and the monomethyl ester of pyruvic acid, potentiate the in vivo beta-cell secretory response to GLP-1 in normal and diabetic rats. Therefore, it was proposed that nutrients susceptible to bypass the site-specific defects of the diabetic beta-cell, could be used to potentiate and/or prolong the insulinotropic action of antidiabetic agents such as GLP-1. In vitro, GLP-1 insulin-like effects on glucose metabolism have been documented in normal and diabetic rat liver, and in rat and human skeletal muscle. In rat and human adipocytes, GLP-1 is lipolytic and/or lipogenic, and also stimulates parameters involved in the glucose metabolism. In liver, muscle and fat, GLP-1 seems to act through specific receptors, apparently different--at least in liver and muscle--in structure or signaling pathway from the pancreatic one. It is proposed that an inositolphosphoglycan might be a second messenger of GLP-1 action in extrapancreatic tissues.
Diabetes Metab 2002 Dec
PMID:Pancreatic and extrapancreatic effects of GLP-1. 1268 38

A series of 20 substituted amides and hydrazides of succinic acid were synthesized and studied with respect to their action upon the blood glucose level in intact rats. The structure-activity relationship is considered. Substances exhibiting maximum hypoglycemic activity were additionally characterized by the acute toxicity and the hypoglycemic effect on the model of alloxan diabetes in rats. It was found that 4-aminobenzoyl hydrazide is more effective and less toxic than the reference compounds metformin and glyclazide.
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PMID:[Hypoglycemic activity of derivatives of succinic acid amides and hydrazides]. 1292 31


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