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

The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool for stimulation of proinsulin biosynthesis and insulin release in animal models of non-insulin-dependent diabetes mellitus. In the present study, either saline or SME (14 mmol/day) was infused for 3 days to control rats, animals injected with streptozotocin during the neonatal period, and Goto-Kakizaki rats with inherited diabetes. The infusion of SME failed to correct the anomalies found in the islets of diabetic rats, namely, a decreased activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired secretory response to various nutrient secretagogues including D-glucose, 2-ketoisocaproate, and the combination of L-leucine and L-glutamine. These findings raise the question of whether a more prolonged administration of SME is required to raise the insulin store and improve the secretory potential of the endocrine pancreas in animals with type 2 diabetes.
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PMID:Enzymatic and secretory activities in pancreatic islets of non-insulin-dependent diabetic rats after short-term infusion of succinic acid monomethyl ester. 771 Jul 67

The present study deals with the insulinotropic action of the dimethyl ester of succinic acid (SAD), considered as a potential tool for the treatment of non-insulin-dependent diabetes mellitus. In the perfused pancreas prepared from either euglycemic rats or animals first infused for 48 hours with a solution of D-glucose, SAD (10 mM) markedly enhanced insulin output evoked by a high concentration of D-glucose (16.7 mM), whether in the absence or presence of glimepiride (0.5 microM). The succinate ester failed, however, to affect glucagon secretion. Thus, SAD indeed displays favourable attributes for stimulation of insulin release in type 2 diabetes, with emphasis on its insulinotropic efficiency at high concentrations of D-glucose in an animal model of B-cell glucotoxicity.
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PMID:Enhancement by succinic acid dimethyl ester of insulin release evoked by D-glucose and glimepiride in the perfused pancreas of normoglycemic and hyperglycemic rats. 818 62

Selected esters of succinic acid are currently under investigation as possible insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus. Novel esters with high insulinotropic efficiency were recently synthesized. The present study concerns the effects of two of these novel esters, namely glycerol-1,2-dimethylsuccinate (2.5 mM) and propanediol-1,2-dimethylsuccinate (1.0 mM), upon the release of insulin and the de novo biosynthesis of peptides in islets from hereditarily diabetic Goto-Kakizaki rats. Whereas D-glucose (2.8 to 16.7 mM) caused a concentration-related stimulation of insulin release in the islets of the diabetic rats, the two esters of succinic acid only increased modestly, and often not significantly, insulin secretion. Nevertheless, they both markedly increased the incorporation of L-[4-3H]phenylalanine into trichloroacetic acid-precipitable material in islets deprived of any other exogenous nutrient. These findings indicate that, at variance with all pharmaceutical agents presently used or proposed as insulin secretagogues in the treatment of type 2 diabetes, glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate, considered as islet cell nutrients, display, in addition to their insulinotropic action, the property of stimulating biosynthetic activity in the endocrine pancreas of animals affected by this disease.
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PMID:Effects of glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate on insulin release and protein biosynthesis in islets of Goto-Kakizaki rats. 943 19

Succinic acid esters are currently under investigation as possible insulinotropic tools in the treatment of noninsulin-dependent diabetes mellitus. The present article introduces three novel nutrient esters and aims mainly to explore, in both normal and GK rats, the secretory response to such esters when tested alone or in combination. It documents that in pancreatic islets from normal rats, methyl acetate (10 mM), which fails to augment basal insulin output, potentiates the secretory response to succinate dimethyl ester (also 10 mM). It also reveals that alpha-D-glucose pentaacetate (alpha GPA) (1.7 mM) stimulates insulin release in the absence of any other exogenous nutrient and even more so in the presence of succinate methyl ester. Moreover, the methyl esters of succinic acid (10 mM), when used together with either methyl acetate or alpha GPA, provoked insulin secretion in islets from diabetic GK rats incubated in the absence of D-glucose, although no significant secretory response of such islets could be detected when each of these agents was tested separately. These findings thus draw attention to the insulinotropic potential in type 2 diabetes of selected combinations of nutrient esters, including a D-glucose ester presumably able to enter into islet cells without requiring the intervention of a hexose carrier.
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PMID:Synergistic insulinotropic action of succinate, acetate, and glucose esters in islets from normal and diabetic rats. 954 40

The nutritional value of glycerol-1,2,3-tris(methylsuccinate), a novel ester of succinic acid with high insulinotropic efficiency both in vitro and in vivo, was assessed in both fed and starved rats. The infusion of the ester, given in a daily amount (1.2 micromol. g body wt-1) well in excess of what could result from its repeated intravenous administration as an insulinotropic agent in non-insulin-dependent diabetes (0.07 micromol. g body wt-1 for each administration), failed to prevent the fall in body weight, liver and muscle glycogen contents, and plasma d-glucose or insulin concentration, as well as the increase in plasma free fatty acid and beta-hydroxybutyrate concentrations caused by starvation. The sole indications that the ester may serve, to a limited extent, as an alternative nutrient in starved rats consisted in a somewhat higher weight of both liver and paraovarian adipose tissue and somewhat higher activity of liver glucokinase in rats receiving the ester than in animals infused with saline. The low nutritional value of this ester thus answers the objection of its possible role as an extrapancreatic nutrient or gluconeogenic precursor in the perspective of its use as an insulinotropic tool in type 2 diabetes.
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PMID:Assessment of the nutritional value of glycerol-1,2, 3-tris(methylsuccinate) in fed and starved rats. 1038 33

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

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.
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PMID:Differential acute and long term actions of succinic acid monomethyl ester exposure on insulin-secreting BRIN-BD11 cells. 1236 22

We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3), which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.
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PMID:Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis. 1600 4

In the present study, the effect of succinic acid monoethyl ester (EMS) on the pattern of lipids and lipoproteins in streptozotocin-nicotinamide induced type 2 diabetes was investigated. Type 2 diabetes was induced in male Wistar rats by single intraperitoneal injection (i.p.) of 45 mg/kg streptozotocin, 15 min after the i.p administration of 110 mg/kg body weight of nicotinamide. The carboxylic nutrient EMS was administered intraperitonially at a dose of 8 micromol/g body weight for 30 days. At the end of experimental period, the effect of EMS on plasma glucose, insulin, thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP) and serum triglycerides (TG), phospholipids (PL), free fatty acids (FFA), total cholesterol (TC), very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and the percentage of antiatherogenic index (AAI) (ratio of HDL-C to total cholesterol) were studied. Administration of EMS to diabetic rats resulted in a significant reduction in the elevated levels of plasma glucose, TBARS and hydroperoxides as well as TG, PL, FFA, TC,VLDL-C and LDC-C levels. The decreased plasma insulin and serum HDL-C and percentage of AAI in diabetic rats were also reversed towards near normal. The effect produced by EMS was compared with metformin, a reference drug. The results indicates that the administration of EMS and metformin to nicotinamide-streptozotocin diabetic rats normalized plasma glucose, insulin concentrations and caused marked improvement in altered lipids, lipoprotein and lipid peroxidation markers during diabetes. Our results show the antihyperlipidemic properties of EMS and metformin in addition to its antidiabetic action. Moreover, the antihyperlipidemic effect could represent a protective mechanism against the development of atherosclerosis.
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PMID:Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes. 1730 96

Authors studied the efficacy of cytoflavin in the correction of cognitive impairment in patients with type 2 diabetes mellitus and the drug influence on the level of brain-derived neurotrophic factor (BDNF) in blood serum. The results of treatment and examination of 60 patients with type 2 diabetes diagnosis have been analyzed. The majority (49-81.6%) of patients initially exhibited light (35-71.4%) and moderate (14-28.6%) cognitive impairments. All patients received standard treatment with oral antidiabetic drugs: metformin monotherapy (26 patients or 43.3%) and combined therapy (metformin + gliclazide, 34 patients or 56.6%). In addition, 30 patients (main group) received a complex metabolic drug cytoflavin daily intravenously (10 mL in 200 mL of 0.9% sodium chloride) for 10 days with transition to the tablet form in a dose of 2 tablets (with 0.6 succinic acid, 0.1 riboxin, 0:05 nicotinamide, 0.01 riboflavin) two times a day for 25 days. The control group (n = 30) consisted of patients who received only basic hypoglycemic therapy. The inclusion of cytoflavin in the scheme of complex treatment of patients with type 2 diabetes ensured a more effective correction of cognitive impairments as compared to the group receiving basic therapy. This is confirmed by the results of neuropsychological testing (MoCA test) and improved optical and spatial activity, attention, abstract thinking, and memory on the average by 14.2% compared to the value before treatment (p < 0.01) in patients of standard treatment group. Patients in the control group showed positive dynamics of same parameters amounted on the average to 7.9%. The study of BDNF in the blood serum showed a significant increase in this index over time in patients who have received cytoflavin (from 1475.13 + 421.26 pg/ml to 1839.44 + 494.78 pg/mL, p < 0.01) in contrast to the control group (1625.41 + 322.53 pg/mL to 1592.04 + 373.47 pg/mL) and revealed positive correlation between the MoCA test and BDNF level in the blood serum for optico-spatial activity (r = 0.589, p < 0.01), naming (animals) (r = 0.346, p < 0.01), attention (r = 0.401, p < 0.01), memory (r=0.595, p< 0.01) and total rating in the test (r = 0.708, p < 0.01). In addition, a negative correlation was revealed between the level of carbohydrate metabolism (HbA1c) and BDNF levels in the blood serum (r = -0.494, p < 0.01) in both groups.
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PMID:[EFFECTIVENESS OF CYTOFLAVIN FOR THE CORRECTION OF COGNITIVE IMPAIRMENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS]. 2701 1


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