Society of university surgeonsGallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice☆
Section snippets
Animals and diets
To study gallbladder myocyte contraction, we obtained 39 lean control C57bl/6J, 19 obese leptin-deficient Lepob, and 20 obese leptin-resistant Lepdb 7-week-old female mice from the Jackson Laboratory (Bar Harbor, Me). The mice were housed in cages of 5 mice each in a light (6am-6pm) and temperature (22°C) controlled environment for 5 weeks. All mice received standard, low-cholesterol chow diet (Ralston Purina, St. Louis, Mo) until 12 weeks of age. At 12 weeks of age, all animals were fasted
Body weight, gallbladder volume, and serum glucose data
Data for body weights, gallbladder volumes, and serum glucose are shown in Fig 2. The body weights of both the leptin-deficient Lepob and leptin-resistant Lepdb mice are greater than twice the size of the lean animals (42.9 and 41.7 vs 16.0 g, P < .001). Similarly, the gallbladder volumes of the obese animals (Lepob 36.2 μL, Lepdb 25.1 μL) were greater than the volumes of the lean animals (8.5 μL, P < .001). In addition, the serum glucose levels were dramatically higher in the obese animals
Discussion
In this study, leptin-deficient (Lepob) and leptin-resistant (Lepdb) obese mice fed a standard chow diet demonstrated significantly greater body weights and higher serum glucose, and had markedly enlarged gallbladders. The gallbladder myocytes from both the leptin-deficient and the leptin-resistant animals were significantly shorter than lean control myocytes. In addition, myocytes from obese animals demonstrated decreased contraction to stimulation by cholecystokinin at 10−8 mol/L
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Cited by (21)
Impaired Gallbladder Motility in Adults with Newly Detected Type 2 Diabetes and Lack of Reversibility after Achieving Euglycemia
2015, Canadian Journal of DiabetesCitation Excerpt :In addition, the effects of hyperglycemia as such could lead to delayed gallbladder emptying. These effects include glycation of proteins, nucleic acids and lipids in the gallbladder wall, causing stiffness of the gallbladder wall and affecting the permeability of CCK (14,20) and poor response of the gallbladder wall to CCK because of decreased CCK receptor numbers or their responses (21,22). After achieving euglycemia, as evidenced by normalization of A1C, GBEF did not improve in patients with diabetes.
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2015, Life SciencesDiabetes and gallstones
2011, Digestive and Liver DiseaseDisruption of the murine protein kinase Cβ gene promotes gallstone formation and alters biliary lipid and hepatic cholesterol metabolism
2011, Journal of Biological ChemistryLeptin Regulates Gallbladder Genes Related to Gallstone Pathogenesis in Leptin-Deficient Mice
2008, Journal of the American College of SurgeonsCitation Excerpt :Gallbladder myocytes also have been shown to have surface CCK-A receptors.15 In addition to the decreased contraction of Lepob gallbladders in muscle baths, we have shown that single gallbladder myocytes of Lepob mice have a decreased response to CCK compared with control mice.6,16 Our current study demonstrates the presence of the gene for the CCK-A receptor in the gallbladder and a relative paucity of CCK-A receptor gene activity in the control Lepob mice, compared with those that received additional leptin.
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Presented at the 65th Annual Meeting of the Society of University Surgeons, St. Louis, Missouri, February 11-14, 2004.
Supported by NIH grant R-01 DK44279.