Palmatine ameliorates high fat diet induced impaired glucose tolerance

BACKGROUND: The impaired glucose tolerance (IGT) is a representative prediabetes characterized by defective glucose homeostasis, and palmatine (PAL) is a natural isoquinoline alkaloid with multiple pharmacological effects. Our study aims to investigate the therapeutic effect of PAL on the impaired glucose tolerance. METHODS: Male Sprague-Dawley rats were used to establish an IGT model with high fat diet (HFD). Oral glucose tolerance test (OGTT) and further biochemical analysis were conducted to determine the effect of PAL on glucose intolerance in vivo. Molecular details were clarified in a cellular model of IGT induced by Palmitate (PA) on INS-1 cells. RESULTS: Our study demonstrated a relief of IGT with improved insulin resistance in HFD induced rats after PAL treatment. Besides, promoted pancreas islets function was validated with significantly increased ß cell mass after the treatment of PAL. We further found out that PAL could alleviate the ß cell apoptosis that accounts for ß cell mass loss in IGT model. Moreover, MAPK signaling was investigated in vivo and vitro with the discovery that PAL regulated the MAPK signaling by restricting the ERK and JNK cascades. The insulin secretion assay indicated that PAL significantly promoted the defective insulin secretion in PA-induced INS-1 cells via JNK rather than ERK signaling. Furthermore, PAL treatment was determined to significantly suppress ß cell apoptosis in PA-induced cells. We thus thought that PAL promoted the PA-induced impaired insulin release by inhibiting the ß; cell apoptosis and JNK signaling in vitro. CONCLUSION: In summary, PAL ameliorates HFD-induced IGT with novel mechanisms.

Effect of Linagliptin versus Metformin on Insulin Secretion, Insulin Sensitivity and Glucose Control in Subjects with Impaired Glucose Tolerance / Efecto de la Linagliptina Frente a la Metformina en la Secreción de Insulina, Sensibilidad a la Insulina y Control de la Glucosa en Sujetos con Intolerancia a la Glucosa

ABSTRACT Aim: The aim of the study is to evaluate the effect of linagliptin versus metformin on insulin secretion, insulin sensitivity and glucose control in patients with impaired glucose tolerance (IGT). Patients and methods: A randomized, double-blind, clinical trial with parallel groups was per-formed on 16 adults with IGT. Lipid profile and haemoglobin (HbA1c) were evaluated prior to and after the intervention. Glucose and insulin were measured at 0, 30, 60, 90 and 120 minutes after a 75-g oral dextrose load. Eight patients received metformin (500 mg) twice a day before meals for three months. The remaining eight patients received placebo (500 mg) in the morning and linagliptin (5 mg) in the evening before meals. The area under the curve (AUC) of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were assessed. Results: After linagliptin administration, a significant decrease in glucose at 90 minutes (10.8 ± 2.6 vs 7.9 ± 2.2 mmol/L, p < 0.05), 120 minutes (8.8 ± 0.9 vs 6.5 ± 2.1 mmol/L, p < 0.05) and AUC of glucose (1168 ± 210 vs 953 ± 207 mmol/L, p < 0.05) were observed. Metformin administration decreased insulin significantly at 0 minutes (94.8 ± 25.8 vs 73.8 ± 24.6 pmol/L, p < 0.05). Conclusion: Three-month administration of linagliptin in patients with IGT decreased glucose at 90 and 120 minutes after a 75-g oral dextrose load and AUC of glucose. Metformin decreased insulin at 0 minutes.

RESUMEN Objetivo: El objetivo del estudio es evaluar el efecto de la linagliptina frente a la metformina en la secreción de insulina, la sensibilidad a la insulina, y el control de la glucosa en pacientes con intolerancia a la glucosa (IG). Pacientes y métodos: Se realizó un ensayo clínico aleatorio de doble ciego con grupos paralelos a 16 adultos con IG. El perfil lipídico y la hemoglobina (Hba1C) se evaluaron antes y después de la intervención. La glucosa y la insulina se midieron a los 0, 30, 60, 90 y 120 minutos después de un carga oral de 75-g dextrosa. Ocho pacientes recibieron metformina (500 mg) dos veces al día antes de las comidas por tres meses. Los ocho pacientes restantes recibieron placebo (500 mg) por la mañana y linagliptina (5 mg) por la noche antes de las comidas. El área bajo la curva (ABC) de la glucosa y la insulina, la secreción total de insulina, la primera fase de la secreción de insulina, y la sensibilidad a la insulina, fueron evaluadas. Resultados: Luego de la administración de la linagliptina, se observó una disminución significativa de la glucosa a los 90 minutos (10.8 ± 2.6 vs 7.9 ± 2.2 mmol/L, p < 0.05), 120 minutos (8.8 ± 0.9 mmol/L p < 0.05) y el ABC de la glucosa (1168 ± 210 vs 953 ± 207 mmol/L, p < 0.05). La administración de metformina redujo significativamente la insulina a los 0 minutos (94.8 ± 25.8 vs 73.8 ± 24.6 pmol/L, p < 0.05). Conclusión: Tres meses de administración de linagliptina en pacientes con IG disminuyó la glucosa a los 90 y 120 minutos después de una carga oral de dextrosa de 75-g y el ABC de la glucosa. La metformina disminuyó la insulina en 0 minutos.

Pioglitazone versus metformin in two rat models of glucose intolerance and diabetes

Insulin resistance has been implicated in the pathogenesis of type 2 diabetes. High fat diets cause insulin resistance. Both metformin and pioglitazone are considered "insulin sensitizers" and used as antihyperglycemic agents for type 2 diabetes treatment. The aim of this study is to Compare pioglitazone and metformin effects on carbohydrate metabolism and insulin sensitivity in diabetic and glucose intolerant rats on high fat diet. Male albino rats were randomized to seven groups. The 1 st group received high carbohydrate diet [control]. The 2 nd, 3 rd and 4 th groups received high sunflower oil diets for 6 weeks and either left untreated, or given pioglitazone or metformin during the last 3 weeks. The 5 th, 6 th, and 7 th groups were made diabetic by STZ injection on day 15 of the 6 weeks-high fat diet regimen. They were either left untreated, or given pioglitazone or metformin during the last 3 weeks. High-fat diet induced glucose intolerance; represented by increase of serum glucose associated with increase in liver glucose-6-phosphatase and decreases in liver glucose-6-phosphate dehydrogenase and glucokinase activities. No significant differences were observed between pioglitazone and metformin. In diabetic rats, both pioglitazone and metformin decreased elevated serum glucose by-30%. Only metformin increased hepatic glycogen, and normalized glucose-6-phosphatase activity. On the other hand, pioglitazone normalized elevated renal glycogen content and increased glucose-6-phosphate dehydrogenase activity. High sunflower oil diet impaired glucose tolerance. Pioglitazone and metformin had comparable effects on estimates of carbohydrate metabolism and insulin sensitivity in high-fat fed rats, but different effects in diabetic rats

Approach to dysglycemia: Do we need to treat impaired glucose tolerance and impaired fasting glucose?

Impaired glucose tolerance [IGT] and impaired fasting glucose [IFG] are not only a surrogate for the state of insulin resistance but are also associated with the microvascular and macrovascular complications traditionally linked to diabetes. They predict an increased risk for death and morbidity due to cardiovascular disease. There is growing evidence that early detection of this state of [pre-diabetes] enables us to limit fehese recognized complications and perhaps to halt the progression to diabetes. For all pre-diabetes patients' life style modifications, emphasizing modest weight loss and moderate physical activity are strongly recommended. Pharmacological intervention may also be necessary. Many studies have shown several drugs, both antidiabetic and nonhypoglycemic agents to be useful. If pharmacological treatment is required, Metformin is considered the first choice because of its safety, tolerability, efficacy and low cost

[Effects of calcitriol [1,25[OH]2D3 treatment on control of glucose intolerance in hemodialysis patients]

Impaired carbohydrate metabolism is a common finding in patients with chronic renal failure. Although intermittent hemodialysis results in a significant improvement of impaired glucose metabolism of uremia, complete normalization did not occur. Vitamin D[3] deficiency, it seems is linked with disturbance of glucose metabolism. A role of vit D in endocrine pancreatic function has been suggested. The aim of this study was to determine the effects of 1,25 [OH]2D3 treatment on glucose tolerance, insulin resistance and beta cell function in hemodialysis patients. Of sixty-five patients with uremia on hemodialysis, twenty -seven who had never been treated with vitamin D or related drugs and without history of diabetes were selected for this study. These patients were randomly divided to two groups, group I were treated with oral calcitriol [0.5 mcg/day] for 8 weeks and group it received placebo for the 8 weeks. In all cases, before and 8 weeks after treatment fasting glucose, insulin, total cholesterol, triglycerides, HDL, LDL, calcium, phosphorous, PTH, HbA1C and blood sugar after 75 gr load of glucose were measured. Insulin resistance [homostatic model assessment-insulin resistance = HOMA-IR] and beta cell function [homostatic model assessment- insulin secretion =HOMA-SECR] were calculated and results of these measurements, before and after 8 weeks, in both groups were compared. In group I, after calcitriol treatment, blood sugar after 75 gr load of glucose [p= 0.045], HOMA -IR [p= 0.035], HbA1C [p=0.00], total cholesterol [p=0.037], and triglycerides [p=0.036] decreased, whereas calcium levels increased, significantly [0.014]; changes in other parameters were not significant. In group II [without treatment] after 8 weeks of observation, fasting blood sugar [p=0.002], HbA1C [p=0.004], HOMA -IR [p=0.036] significantly increased and beta cell function decreased significantly [p= 0.032]; again alterations in other parameters were not significant. These results seem to confirm that the active form of vitamin D influences glucose and lipid metabolism, by the improvement of insulin resistance

Effects of ca2+ entry blockers and an intracellular ca2+ antagonist on glucose tolerance and insulin secretion in rats

The effects of Ca2+ entry blockers: Isradipine [5 mg/kg i.p.] and flunarizine HCl [10 mg/kg i.p.] as well as the intracellular Ca2+ antagonist, dantrolene Na [5 mg/kg i.p.] were studied on blood glucose levels, insulin secretion and liver glycogen content during an oral glucose tolerance test in rats. Isradipine markedly increased plasma glucose and significantly reduced plasma insulin levels, which was accompanied by a marked increase in liver glycogen content. Isradipine-induced glucose intolerance was associated with a decreased pancreatic secretory activity as evidenced by lowered insulinogenic indices. Flunarizine HCl produced significant increase in plasma glucose level 1 hour after drug administration which was associated with decreased insulinogenic index, while the drug had no effect on plasma insulin levels or liver glycogen content. Dantrolene Na increased plasma glucose level 1 hour after drug treatment, but it failed to significantly alter plasma insulin level, insulinogenic index or liver glycogen content. In conclusion, the data suggested that the calcium entry blockers [isradipine and flunarizine] impair glucose tolerance in rats and confirm the in vitro results on the isolated perfused rat pancreas. Studies have also shown that isradipine is more potent hyperglycemic agent than flunarizine. Also, it is a potent inhibitor of insulin secretion under glucose-stimulated conditions