Nigella sativa stimulates insulin secretion from isolated rat islets and inhibits the digestion and absorption of (CH2O)n in the gut

Nigella sativa seeds are traditionally reputed as possessing anti-diabetic properties. As a result, we aim to explore the mechanism of its anti-hyperglycemic activity. The present study uses various experimental designs including gastrointestinal (GI) motility, intestinal disaccharidase activity and inhibition of carbohydrate digestion and absorption in the gut. The animals used as type 2 diabetic models were induced with streptozotocin to make them as such. Oral glucose tolerance test was performed to confirm that the animals were indeed diabetic. The extract reduced postprandial glucose, suggesting it interfered with glucose absorption in the gut. It also improved glucose (2.5g/kg, b/w) tolerance in rats. Furthermore, treatment with N. sativa produced a significant improvement in GI motility, while reduced disaccharidase enzyme activity in fasted rats. The extract produced a similar effect within an acute oral sucrose (2.5g/kg, b/w) load assay. Following sucrose administration, a substantial amount of unabsorbed sucrose was found in six different parts of the GI tract. This indicates that N. sativa has the potentiality to liberate GI content and reduce or delay glucose absorption. A potential hypoglycemic activity of the extract found in insulin release assay, where the extract significantly improved insulin secretion from isolated rat islets. These concluded present findings give rise to the implication that N. sativa seeds are generating postprandial anti-hyperglycemic activity within type 2 diabetic animal models via reducing or delaying carbohydrate digestion and absorption in the gut as well as improving insulin secretion in response to the plasma glucose.

Ethanolic Extract ofButea monospermaLeaves Elevate Blood Insulin Level in Type 2 Diabetic Rats, Stimulate Insulin Secretion in Isolated Rat Islets, and Enhance Hepatic Glycogen Formation

We measured a vast range of parameters, in an attempt to further elucidate previously claimed antihyperglycemic activity ofButea monosperma. Our study clearly negates the possibility of antidiabetic activity by inhibited gastrointestinal enzyme action or by reduced glucose absorption. Reduction of fasting and postprandial glucose level was reconfirmed (P<0.05). Improved serum lipid profile via reduced low density lipoprotein (LDL), cholesterol, triglycerides (TG), and increased high density lipoprotein (HDL) was also reestablished (P<0.05). Significant insulin secretagogue activity ofB. monospermawas found in serum insulin assay ofB. monospermatreated type 2 diabetic rats (P<0.01). This was further ascertained by our study on insulin secretion on isolated rat islets (P<0.05). Improved sensitivity of glucose was shown by the significant increase in hepatic glycogen deposition (P<0.05). Hence, we concluded that antihyperglycemic activity ofB. monospermawas mediated by enhanced insulin secretion and enhanced glycogen formation in the liver.

Translational Control of Glucose-Induced Islet Amyloid Polypeptide Production in Pancreatic Islets

Dysfunctional islet amyloid polypeptide (IAPP) biosynthesis and/or processing are thought contribute to formation of islet amyloid in type 2 diabetes. However, it is unclear how normal pro-IAPP biosynthesis and processing are regulated to be able to define such dysfunction. Here, it was found that acute exposure to high glucose concentrations coordinately regulated the biosynthesis of pro-IAPP, proinsulin, and its proprotein convertase PC1/3 in normal isolated rat islets, without affecting their respective mRNA levels. Pro-7B2 biosynthesis, like that of pro-PC2, did not appreciably change, but this was likely due to a much higher expression in pancreatic α-cells masking glucose regulation of their biosynthesis in β-cells. Biosynthesis of pro-SAAS, the putative PC1/3 chaperone, was unaffected by glucose, consistent with its scarce expression in β-cells. We conclude that translational control of pro-IAPP biosynthesis, in parallel to the pro-PC1/3, pro-PC2, and pro-7B2 proprotein-processing endopeptidases/chaperones, is the predominate mechanism to produce IAPP in islet β-cells.

Binding of activating transcription factor 6 to the A5/Core of the rat insulin II gene promoter does not mediate its transcriptional repression

Pancreatic β-cells have a well-developed endoplasmic reticulum due to their highly specialized secretory function to produce insulin in response to glucose and nutrients. It has been previously reported that overexpression of activating transcription factor 6 (ATF6) reduces insulin gene expression in part via upregulation of small heterodimer partner. In this study, we investigated whether ATF6 directly binds to the insulin gene promoter, and whether its direct binding represses insulin gene promoter activity. A bioinformatics analysis identified a putative ATF6 binding site in the A5/Core region of the rat insulin II gene promoter. Direct binding of ATF6 was confirmed using several approaches. Electrophoretic mobility shift assays in nuclear extracts from MCF7 cells, isolated rat islets and insulin-secreting HIT-T15 cells showed ATF6 binding to the native A5/Core of the rat insulin II gene promoter. Antibody-mediated supershift analyses revealed the presence of both ATF6 isoforms, ATF6α and ATF6β, in the complex. Chromatin immunoprecipitation assays confirmed the binding of ATF6α and ATF6β to a region encompassing the A5/Core of the rat insulin II gene promoter in isolated rat islets. Overexpression of the active (cleaved) fragment of ATF6α, but not ATF6β, inhibited the activity of an insulin promoter–reporter by 50%. However, the inhibitory effect of ATF6α was insensitive to mutational inactivation or deletion of the A5/Core. Therefore, although ATF6 binds directly to the A5/Core of the rat insulin II gene promoter, this direct binding does not appear to contribute to its repressive activity.