Apc a-00121-bile acid depletion
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Transcript of Apc a-00121-bile acid depletion
a-00121
Dr. Robert RUTLEDGE
Title of Paper: BILE ACID DEPLETION WITH GASTRO-
INTESTINAL BYPASS DECREASES HGB-A1C & SERUM
GLUCOSE AND IMPROVES INSULIN SENSITIVITY.
Nationality: United States of America
Position: Director
Department: Surgery
Organization: Center For Laparoscopic Obesity Surgery
Tel: +1-702 714 0011
E-mail: [email protected]
BILE ACID DEPLETION
WITH
GASTRO-INTESTINAL BYPASS
DECREASES HGB-A1C &
SERUM GLUCOSE AND
IMPROVES INSULIN SENSITIVITY
Robert RUTLEDGE1
1Director, Surgery, Center For Laparoscopic
Obesity Surgery, United States of America
Introduction
• Long term studies show deterioration of the initial improvement in diabetes after bariatric surgery over time.
• New research shows that Bile Acids (BAs) are signaling molecules, with systemic endocrine functions.
• Decrease in BAs can decrease fat absorption, triglyceride, cholesterol, energy, and
• HORMONALLY ACT improve glucose homeostasis.
Bile Acid Binding
Colesevelam a bile acid sequestrant
Manipulation of the bile acid pool plays a role in glucose homeostasis
Farnesoid X receptor (FXR)
• The bile acid receptor (BAR), also known as Farnesoid X receptor (FXR) is a nuclear receptor
• FXR is expressed at high levels in the liver and intestine.
• FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes
• The nuclear BA receptor farnesoid X
receptor (FXR) regulates pathways in BA,
lipid, glucose, and energy metabolism,
which become dysregulated in obesity.
Bile Acids & FXR
• Decrease in Bile Acids Decreases FXR attenuates body weight gain and reduces adipose tissue mass in animal and human models.
• Glucose homeostasis is improved as a result of an enhanced glucose clearance and adipose tissue insulin sensitivity.
• Decreasing elevated plasma BA concentrations in obese mice by administration of the BA sequestrant colesevelam improved glucose homeostasis in a FXR-dependent manner,
Bile acids and signal transduction:
Role in glucose homeostasis
• Regulation of glucose metabolism by bile acids
• Regulates Farnesoid X receptor (FXR), which can stimulate the insulin receptor (IR)
Methods:
• Reviewed literature on
• Bile Acids as critical factors in
• Glucose homeostasis and
• Recent publications on
• Bile Acid Pool manipulation in the
• Management of Diabetes.
Methods
• Review of data showing that duodenal bypass as part of
• Combined Gastro-Intestinal Procedures (CGIPs) decrease BA pool (Shorter Bowel)
• decreasing weight, lipids,
• Hormonal Effect: improves insulin sensitivity and glucose homeostasis
• Further support to the importance to the bypass component of durable weight loss procedures.
Results
• Bile acids are known to facilitate digestion and absorption of lipids and regulate cholesterol homeostasis.
• It has now become clear that bile acids are critical hormones involved in activation of various signaling pathways, including triglyceride, cholesterol, glucose, and energy homeostasis.
Results
• Studies show
• Decrease in the bile acid pool
• Results in decreases in
hemoglobin A1c, glucose levels
and
• Improved insulin sensitivity.
Results
• Recent studies from Korea and China have
shown that in comparison to
• Primary Gastric Procedures (PGP) the use
• Combined Gastro-Intestinal Procedures
(CGIP) improve the success in the resolution
of diabetes.
• Combined procedures include duodenal
bypass which leads to decrease in bile acid
pool.
Conclusions:
• Bile acids regulate
triglyceride, cholesterol, glucose, and
energy homeostasis. (OLD)
• Decreased Bile acid pool size decreases
fat absorption, cholesterol and
triglycerides. (OLD)
Conclusions
• Bile Acids are also Gut Hormones
(New)
• Decreaseing Bile Acids (through
modulation of FXR and TGR5)
• Improves Glucose Homeostasis (New)
• Manipulation of Bile Acids Hormonally
can be treatment of Diabetes
(New, Welchol)