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2003 Abstract: Diabetes Correlates with Abnormal Gallbladder Contractility in Leptin-Related Murine Obesity
AbstractID – 100382 Presentation Preference – Oral
Resident's Prize – Resident's Prize
Category – Biliary (S14)  

Diabetes Correlates with Abnormal Gallbladder Contractility in Leptin-Related Murine Obesity

Khoi Q Tran, Matthew I Goldblatt, Deborah A Swartz-Basile, Carol L Svatek, Attila Nakeeb, Henry A Pitt, Milwaukee, WI.

Obesity is associated with multiple comorbidities including hyperlipidemia, diabetes and gallstones. However, the interaction among these various modalities remains unclear. We have recently demonstrated that two strains of obese mice with absent (Lepob) and very high (Lepdb) serum leptin, respectively, have normal (Lepob) and low (Lepdb) biliary lipids. Both of these leptin-related murine models of obesity have impaired biliary motility and high serum lipids which correlate inversely with gallbladder muscle response. Both leptin-deficient (Lepob) and leptin-resistant (Lepdb) mice are also diabetic, and diabetes has been recently documented to be a risk factor for gallstone formation. Therefore, we tested the hypothesis that serum glucose would correlate with gallbladder contractility.
Thirty-four lean control (C57BL/6J), 10 lean heterozygous leptin-deficient (Lephet), 18 obese homozygous leptin-deficient (Lepob) and 12 obese homozygous leptin-resistant (Lepdb) mice were fed a nonlithogenic CHOW diet for four weeks. All animals were then fasted overnight and underwent cholecystectomy. In vitro gallbladder responses to cholecystokinin (CCK 10-8 M), acetylcholine (ACh 10-5 M) and neuropeptide Y (NPY 10-6 M) were measured. Serum glucose levels (mg/dl) were determined in pooled blood from an additional 221 lean control, 160 lean Lephet, 68 obese Lepob and 78 obese Lepdb mice. Serum glucose was correlated with normalized gallbladder responses for CCK, ACh and NPY using Pearson's correlation (r). Results are presented in the table.
These data suggest that in vitro murine gallbladder responses to cholecystokinin, acetylcholine and neuropeptide Y are inversely correlated with serum glucose. We conclude that hyperglycemia in obese mice with leptin dysfunction is associated with poor gallbladder contractility which, in turn, may contribute to the association between obesity and gallstone formation.

 

 

Serum Glucose and Gallbladder Responses to Neurotransmitters

 

Glucose 

CCK 

ACh 

NPY 

Lean control 

193 ± 9 

1.00 ± 0.08 

0.42 ± 0.03 

0.19 ± 0.02 

Lean Lephet 

116 ± 9 

0.62 ± 0.10 

0.33 ± 0.07 

0.13 ± 0.03 

Obese Lepob 

428 ± 23 

0.43 ± 0.06 

0.18 ± 0.02 

0.07 ± 0.01 

Obese Lepdb 

496 ± 25 

0.42 ± 0.11 

0.15 ± 0.05 

0.04 ± 0.01 

Correlation 

 

r = -0.46 

r = -0.54 

r = -0.50 

Significance 

 

p < 0.001 

p < 0.001 

p < 0.001 

 

 

 




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