Effect of benfluorex on insulin secretion and insulin action in streptozotocin-diabetic rats

In an ex situ organ perfusion system, that of the isolated nonrecirculating joint perfusion of rat small intestine and liver, insulin infused into the portal vein increased intestinal glucose absorption. This insulin action against the bloodstream can be blocked by TTX, indicating a propagation of the insulin signal via hepatoenteral nerves, which conforms with previous studies with atropine and carbachol. Insulin action could also be mimicked by dibutyryl cAMP (DBcAMP) acting directly on the absorptive enterocytes. Because autonomic neuropathy is a common late complication of diabetes mellitus, the possible impairment of these nerves in the diabetic state was studied in streptozotocin-diabetic rats. In the isolated joint intestine-liver perfusion, glucose was applied as a bolus into the lumen; its absorption was measured in the portal vein. In 5-day diabetic as well as in control rats, portal insulin, arterial carbachol, and arterial DBcAMP increased intestinal glucose absorption. In 3-mo diabetic rats portal insulin and arterial carbachol failed to stimulate glucose absorption, whereas arterial DBcAMP still did so, indicating an undisturbed function of the absorptive enterocytes. The lack of an effect of portal insulin and arterial carbachol and the unchanged action of DBcAMP in the chronically diabetic rats indicated that the signaling chain via the hepatoenteral nerves was impaired, which is in line with a diabetic neuropathy.

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Antihyperglycaemic activity of Asparagus racemosus roots is partly mediated by inhibition of carbohydrate digestion and absorption, and enhancement of cellular insulin action

British Journal Of Nutrition ◽

10.1017/s0007114511004284 ◽

2011 ◽

Vol 107 (9) ◽

pp. 1316-1323 ◽

Cited By ~ 15

Author(s):

J. M. A. Hannan ◽

Liaquat Ali ◽

Junaida Khaleque ◽

Masfida Akhter ◽

Peter R. Flatt ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Action ◽

Liver Glycogen ◽

Serum Glucose ◽

Diabetic Rats ◽

Asparagus Racemosus ◽

Sucrose Content ◽

Ethanol Extracts ◽

Oxidant Status ◽

Carbohydrate Digestion

Asparagus racemosus roots have been shown to enhance insulin secretion in perfused pancreas and isolated islets. The present study investigated the effects of ethanol extracts of A. racemosus roots on glucose homeostasis in diabetic rats, together with the effects on insulin action in 3T3 adipocytes. When administered orally together with glucose, A. racemosus extract improved glucose tolerance in normal as well as in two types of diabetic rats. To investigate the possible effects on carbohydrate absorption, the sucrose content of the gastrointestinal tract was examined in 12 h fasted rats after an oral sucrose load (2·5 g/kg body weight). The extract significantly suppressed postprandial hyperglycaemia after sucrose ingestion and reversibly increased unabsorbed sucrose content throughout the gut. The extract also significantly inhibited the absorption of glucose during in situ gut perfusion with glucose. Furthermore, the extract enhanced glucose transport and insulin action in 3T3-L1 adipocytes. Daily administration of A. racemosus to type 2 diabetic rats for 28 d decreased serum glucose, increased pancreatic insulin, plasma insulin, liver glycogen and total oxidant status. These findings indicate that antihyperglycaemic activity of A. racemosus is partly mediated by inhibition of carbohydrate digestion and absorption, together with enhancement of insulin secretion and action in the peripheral tissue. Asparagus racemosus may be useful as a source of novel antidiabetic compounds or a dietary adjunct for the management of diabetes.

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Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway

Journal of Endocrinology ◽

10.1677/joe-07-0184 ◽

2007 ◽

Vol 195 (1) ◽

pp. 105-112 ◽

Cited By ~ 64

Author(s):

Muhammed Yusuf Ali ◽

Matthew Whiteman ◽

Chian-Ming Low ◽

Philip K Moore

Keyword(s):

Insulin Secretion ◽

Hydrogen Sulphide ◽

Recent Observation ◽

Diabetic Rats ◽

Β Cells ◽

Naturally Occurring ◽

Streptozotocin Diabetic Rats ◽

Channel Dependent ◽

Dependent Pathway ◽

Insight Into

Hydrogen sulphide (H2S), a naturally occurring gas exerts physiological effects by opening KATP channels. Anti-diabetic drugs (e.g. glibenclamide) block KATP channels and abrogate H2S-mediated physiological responses which suggest that H2S may also regulate insulin secretion by pancreatic β-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 μM) and the KATP channel-driven pathway of insulin secretion was tracked with various fluorescent probes. The concentration of insulin released from HIT-T15 cells decreased significantly after NaHS exposure and this effect was reversed by the addition of glibenclamide (10 μM). Cell viability and intracellular ATP and glutathione (GSH) levels remained unchanged, suggesting that changes in insulin secretion were not ATP linked or redox dependent. Through fluorescence imaging studies, it was found that K+ efflux occurs in cells exposed to NaHS. The hyperpolarised cell membrane, a result of K+ leaving the cell, prevents the opening of voltage-gated Ca2+ channels. This subsequently prevents Ca2+ influx and the release of insulin from HIT-T15 cells. This data suggest that H2S reduces insulin secretion by a KATP channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H2S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H2S production in streptozotocin-diabetic rats.

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