The triggering pathway, the metabolic amplifying pathway, and cellular transduction in regulation of glucose-dependent biphasic insulin secretion.

Introduction: Insulin secretion is a highly regulated process critical for maintaining glucose homeostasis. This abstract explores the intricate interplay between three essential pathways: The Triggering Pathway, The Metabolic Amplifying Pathway, and Cellular Transduction, in orchestrating glucose-dependent biphasic insulin secretion.Mechanism: During the triggering pathway, glucose metabolism in pancreatic beta-cells leads to ATP production, closing ATP-sensitive potassium channels and initiating insulin exocytosis. The metabolic amplifying pathway enhances insulin secretion via key metabolites like NADH and glutamate, enhancing calcium influx and insulin granule exocytosis. Additionally, the cellular transduction pathway involves G-protein coupled receptors and cyclic AMP, modulating insulin secretion.Result and Conclusion: These interconnected pathways ensure a dynamic insulin response to fluctuating glucose levels, with the initial rapid phase and the subsequent sustained phase. Understanding these pathways' complexities provides crucial insights into insulin dysregulation in diabetes and highlights potential therapeutic targets to restore glucose-dependent insulin secretion.

Preformulation screening of lipids using solubility parameter concept in conjunction with experimental research to develop ceftriaxone loaded nanostructured lipid carriers

Abstract Development of ceftriaxone loaded nanostructured lipid carriers to increase permeability of ceftriaxone across uninflamed meninges after parenteral administration. Lipids were selected by theoretical and experimental techniques and optimization of NLCs done by response surface methodology using Box-Behnken design. The Δδt for glyceryl monostearate and Capryol90 were 4.39 and 2.92 respectively. The drug had maximum solubility of 0.175% (w/w) in glycerol monostearate and 2.56g of Capryol90 dissolved 10mg of drug. The binary mixture consisted of glyceryl monostearate and Capryol90 in a ratio of 70:30. The optimized NLCs particle size was 130.54nm, polydispersity index 0.28, % entrapment efficiency 44.32%, zeta potential -29.05mV, and % drug loading 8.10%. In vitro permeability of ceftriaxone loaded NLCs was 5.06x10-6 cm/s; evidently, the NLCs pervaded through uninflamed meninges, which, was further confirmed from in vivo biodistribution studies. The ratio of drug concentration between brain and plasma for ceftriaxone loaded NLCs was 0.29 and that for ceftriaxone solution was 0.02. With 44.32% entrapment of the drug in NLCs the biodistribution of ceftriaxone was enhanced 7.9 times compared with that of ceftriaxone solution. DSC and XRD studies revealed formation of imperfect crystalline NLCs. NLCs improved permeability of ceftriaxone through uninflamed meninges resulting in better management of CNS infections.

Treatment effect of l-Norvaline on the sexual performance of male rats with streptozotocin induced diabetes.

Sexual impairment is an established risk factor in diabetes mellitus affecting about 75% of male diabetic population. In diabetes overexpression of arginase leads to decreased production of NO and diminished erectile response. Inhibition of arginase enzyme can lead to improvement in diabetes induced sexual dysfunction. In the present study diabetes mellitus was induced in adult male rats by intraperitoneal injection of single dose of streptozotocin (65mg/kg) in 0.1M Citrate buffer pH 4.5 and after 72h fasting serum glucose level was checked by glucose oxidase-peroxidase method and those animals showing FSG above 250mg/dl were selected. Diabetic animals were divided into four groups comprising six animals in each. l-Norvaline, potent arginase inhibitor was administered at a dose of 10mg/kg ip to the different groups of diabetic animals for a period of 30 days. Sildenafil at a dose of 5mg/kg orally was used as a standard drug. Mating behavior tests were performed at 0, 15th and 30th days. After 30 days, various biochemical and hormonal parameters (nitrates, LDH, urea, testosterone), testicular parameters (total protein, nitrates, LDH, total cholesterol, LDL, triglycerides, VLDL, HDL) were evaluated to find out the effect of l-Norvaline in sexual impairment. Sperm analysis was also carried out for the treated rats. l-Norvaline showed significant improvement in serum nitrates, urea, LDH, testosterone and testicular protein level as compared with diabetic group. It also improved sperm motility, count and viability in diabetic rats. Sildenafil showed no improvement in above parameters except restoration in serum nitrates level.

Ferula asafoetida: Traditional uses and pharmacological activity.

Ferula asafoetida is herbaceous plant of the umbelliferae family. It is oleo gum resin obtained from the rhizome and root of plant. This spice is used as a digestive aid, in food as a condiment and in pickles. It is used in modern herbalism in the treatment of hysteria, some nervous conditions, bronchitis, asthma and whooping cough. It was at one time employed in the treatment of infantile pneumonia and flatulent colic. The gum resin is antispasmodic, carminative, expectorant, laxative, and sedative. The volatile oil in the gum is eliminated through the lungs, making this an excellent treatment for asthma. The odor of asafoetida is imparted to the breath, secretions, flatus, and gastric eructations. Its properties are antispasmodic, expectorant, stimulant, emmenagogue and vermifuge. Asafoetida has also been used as a sedative. It also thins the blood and lowers blood pressure. It is widely used in India in food and as a medicine in Indian systems of medicine like ayurveda. Asafoetida has been held in great esteem among indigenous medicines, particularly in Unani system from the earliest times.

Anti-anxiety activity of Coriandrum sativum assessed using different experimental anxiety models.

Interest in alternative medicine and plant-derived medications that affect the "mind" is growing. The aim of present study was to explore the anti-anxiety activity of hydroalcoholic extract of Coriandrum sativum (Linn.) using different animal models (elevated plus maze, open field test, light and dark test and social interaction test) of anxiety in mice. Diazepam (0.5 mg/kg) was used as the standard and dose of hydroalcoholic extract of C. sativum fruit (50, 100 and 200 mg/kg) was selected as per OECD guidelines. Results suggested that extract of C. sativum at 100 and 200 mg/kg dose produced anti-anxiety effects almost similar to diazepam, and at 50 mg/kg dose did not produce anti-anxiety activity on any of the paradigm used. Further studies are needed to identify the anxiolytic mechanism(s) and the phytoconstituents responsible for the observed central effects of the hydroalcoholic extract of C. sativum.

Assessment of antidiabetic potential of Cinnamomum tamala leaves extract in streptozotocin induced diabetic rats.

OBJECTIVE: To establish the effect of Cinnamomum tamala leaves extract on diabetes and diabetes induced dyslipidemia in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced by a single intravenous injection of streptozotocin (50 mg/kg body weight). Group I and II were kept as control and diabetic control respectively. And group III was further treated with ethanolic leaf extract of C. tamala (200 mg/kg body weight, orally) for a period of 40 days. Oral glucose tolerance test was performed before starting the experiment and blood glucose level was estimated. Statistical analysis was performed using one-way Analysis of Variance (using Statistical Package for the Social Sciences [SPSS] version 10.0) and student's 't'- test (Sigma Plot version 8.0). The values of P < 0.05 were considered as statistically significant. RESULTS: Treatment of diabetic animals with Cinnamomum tamala extract significantly lowered the blood glucose level, and maintained body weight and lipid-profile parameters towards near normal range. CONCLUSION: The extract exhibited antidiabetic and antidyslipidemic effect. Further, chemical and pharmacological investigations are required to elucidate the exact mechanism of action of this extract and to isolate the active principles responsible for these effects.