Incretin secretion stimulated by ursodeoxycholic acid in healthy subjects and diabetics

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 834-867-Islet Biology
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-863
Masanori Murakami*1, Naoko Une1, Maiko Nishizawa1, Sayaka Suzuki1, Sachio Takekawa1, Fumiko Iwashima1, Hideki Ito2, Yoshihiro Ogawa3 and Toshiyuki Horiuchi1
1Tokyo Metropolitan Health Medical Treatment Corporation Toshima Hospital, Tokyo, Japan, 2Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan, 3Tokyo Med and Dental University, Tokyo, Japan
Bile acids play an important role in post-prandial glucose metabolism by stimulating release of glucagon-like peptide-1 (GLP-1) via the G-protein-coupled receptor TGR5, which is expressed in intestinal L cells. Thus, bile acid sequestrants are expected to stimulate secretion of endogenous GLP-1 through TGR5. We investigated incretin and insulin secretion after a meal with and without ursodeoxycholic acid (UDCA), a widely used therapeutic agent in liver diseases, in non-diabetic Japanese subjects. As we previously showing, UDCA intake resulted in higher GLP-1 secretion and lower blood glucose in 7 non-diabetic subjects with statistically significant difference (1). Tendency to higher insulin secretion was observed in UDCA stimulated subjects, but not with statistically significance. For further investigation about diabetic subjects, we recruited 7 diabetic subjects, and they were a mean age of 76.9 ± 3.1 years (range 62-88), their average BMI was 25.3 ± 1.8 (range 19.2-31.3), and their average HbA1c was 6.57 ± 0.11% (range 6.1-7.0). We found that UDCA intake did not induce higher GLP-1 secretion (area under the curve [AUC] of 0–180 min after meal without UDCA, 1001 ± 222 mmol·min/l; with UDCA, 1060 ± 324 mmol·min/l, P > 0.05), lower blood glucose (AUC of 0–180 min without UDCA, 29552 ± 1823 mg·min/dl; with UDCA, 28129 ± 1550 mg·min/dl, P > 0.05) and lower insulin secretion (AUC of 0–180 min without UDCA, 5063 ± 1459 μIU·min/ml; with UDCA, 5493 ± 1961 μIU·min/ml, P > 0.05). Although UDCA was a stimulator of GLP-1 secretion and has a hypoglycemic effect in non-diabetic subjects, we found that effect of UDCA was diminished in diabetic subjects. These results suggest that the effect of UDCA could be seen in healthy people, who have enough GLP-1 secretion ability. Ours is the first report investigating kinetics of GLP-1 secretion, insulin secretion and blood glucose in response to UDCA intake in both non-diabetic and diabetic subjects.

(1) Murakami M et al., SpringerPlus 2013; 2:20.

Nothing to Disclose: MM, NU, MN, SS, ST, FI, HI, YO, TH

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm