scholarly journals Effect of Ezetimibe on Insulin Secretion in db/db Diabetic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yong Zhong ◽  
Jun Wang ◽  
Ping Gu ◽  
Jiaqing Shao ◽  
Bin Lu ◽  
...  

Objective. To investigate the effect of ezetimibe on the insulin secretion in db/db mice.Methods. The db/db diabetic mice aged 8 weeks were randomly assigned into 2 groups and intragastrically treated with ezetimibe or placebo for 6 weeks. The age matched db/m mice served as controls. At the end of experiment, glucose tolerance test was performed and then the pancreas was collected for immunohistochemistry. In addition, in vitro perfusion of pancreatic islets was employed for the detection of insulin secretion in the first phase.Results. In the ezetimibe group, the fasting blood glucose was markedly reduced, and the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lowered when compared with those in the control group (P<0.05). At 120 min after glucose tolerance test, the area under curve in the ezetimibe group was significantly smaller than that in the control group (P<0.05), but theAUCINS0−30was markedly higher. In vitro perfusion of pancreatic islets revealed the first phase insulin secretion was improved. In addition, the insulin expression in the pancreas in the ezetimibe group was significantly increased as compared to the control group.Conclusion. Ezetimibe can improve glucose tolerance, recover the first phase insulin secretion, and protect the function ofβcells in mice.

1998 ◽  
Vol 83 (9) ◽  
pp. 3350-3356 ◽  
Author(s):  
Bo Ahrén ◽  
Giovanni Pacini

This study examined whether insulin secretion, insulin sensitivity, glucose effectiveness (SG), and hepatic extraction (HE) of insulin are altered by age when glucose tolerance is normal. A frequently sampled iv glucose tolerance test was performed in 20 elderly (E, 10/10 male/female, all 63 yr old) and in 20 young subjects (Y, 10/10 male/female, all 27 yr old), who were similar in body mass index and 2-h blood glucose during oral glucose tolerance test. E exhibited impaired glucose elimination (iv tolerance index, 1.31 ± 0.10 vs. 1.70 ± 0.12% min−1; P = 0.019). First-phase insulin secretion and SI did not differ between the groups, whereas E had lower glucose sensitivity of second-phase insulin secretion (0.40 ± 0.07 vs. 0.70 ± 0.08 (pmol/L)min−2/(mmol/L), P = 0.026), lower SG, 0.017 ± 0.002 vs. 0.025± 0.002 min−1, P = 0.004), and higher HE (81.3 ± 2.4 vs. 73.2 ± 2.1%, P = 0.013). Across both groups, SG correlated positively with glucose tolerance index (r = 0.58, P &lt; 0.001) and negatively with HE (r =− 0.54, P &lt; 0.001). Plasma leptin and glucagon did not change by age, whereas plasma pancreatic polypeptide (PP) was higher in E (122 ± 18 vs.66 ± 6 pg/mL, P = 0.004). PP did not, however, correlate to any other parameter. We conclude that E subjects with normal oral glucose tolerance have reduced SG, impaired second-phase insulin secretion, and increased HE, whereas SI and first-phase insulin secretion seem normal. SG seems most related to age-dependent impairment of glucose elimination, whereas leptin, glucagon, and PP do not seem to contribute.


1989 ◽  
Vol 35 (7) ◽  
pp. 1482-1485 ◽  
Author(s):  
E A de Leacy ◽  
D M Cowley

Abstract Fifty consecutive pregnant patients referred for a glucose-tolerance test were classified on the basis of increasing (n = 20) or decreasing (n = 28) hematocrit after an oral 75-g glucose load. (The hematocrit did not change in the other two patients.) Patients with increasing hematocrit, a response previously seen in patients with the dumping syndrome, showed significantly flatter increases in glucose concentrations in plasma after the load. The mean decrease in the concentration of phosphate in plasma, measured as an index of glucose uptake by cells, was significantly less (P less than 0.05) 2 h after the load in the group with flatter glucose responses, suggesting that the flat response is ascribable to poor glucose absorption rather than to an exaggerated insulin response. These results indicate that the oral glucose-tolerance test stresses the pancreatic islets differently in different pregnant subjects, owing to individual variations in the gastrointestinal handling of the glucose load. Consequently, patients may give a "normal" result who might otherwise become hyperglycemic after normal meals. We suggest that alternative screening procedures be investigated to assess pregnant patients postprandially.


1999 ◽  
Vol 162 (1) ◽  
pp. 87-93 ◽  
Author(s):  
T Johansen ◽  
M Deckert ◽  
T Mandrup-Poulsen ◽  
K Malmlof

Growth hormone (GH) can oppose the catabolic effects of glucocorticoids. However, both hormones have adverse effects on carbohydrate metabolism. Here we examined the interactive effects of GH and the glucocorticoid methylprednisolone (MP) on glucose tolerance, insulin resistance and [3H]2,6-deoxyglucose uptake of peripheral tissues in rats. Female Wistar rats received either saline, GH (2.7 mg/kg), MP (5.0 mg/kg) or GH+MP. After 7 days treatment, animals were subjected to an i.v. glucose tolerance test. In a second experiment, animals treated as above were anesthetized and injected with human insulin (0.5 U/kg), [3H]2,6-deoxyglucose (500 microCi/kg), and [14C]mannitol (25 microCi/kg), to estimate insulin resistance and [3H]2,6-deoxyglucose uptake in fat and muscle. Weight gain in controls was 7.6+/-1.7 g, while GH treatment increased the mean body weight by 18.7+/-2.2 g (P<0.0002) and MP inhibited weight gain down to 0.0+/-1.0 g (P<0.004). This drop in weight gain was reversed back to normal when GH was given in combination with MP. After a glucose tolerance test no significant differences in glucose area under the curve were detected when comparing individual groups with the control group, but samples taken just before this test revealed that basal insulin was significantly elevated in the group treated with GH (174+/-27 pM, P<0.008), or GH+MP (209+/-21 pM, P<0.004), when compared with controls (107+/-17 pM). MP alone had no effect (122+/-19, P<0.3). After an i.v. bolus of insulin the group receiving GH+MP had a significantly (P<0.007) higher level of circulating glucose compared with controls (6.5+/-0.3 mM vs 4.4+/-0.7 mM). Despite this, there were no differences in peripheral glucose uptake between the two groups. In conclusion this study shows that a combined administration of GH and MP decreases the potency by which insulin decreases circulating glucose levels, but that peripheral tissues are not primarily involved in this insulin resistance.


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