Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice.
BACKGROUND
Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lepob) and leptin-resistant (Lepdb) mice are hyperglycemic and have enlarged gallbladders with diminished response in vitro to cholecystokinin (CCK) and acetylcholine (ACh). Whether this phenomenon is secondary to hyperosmolar myocytes and/or decreased neuromuscular transmission remains unclear. We hypothesize that myocytes from Lepob and Lepdb obese mice would not respond normally to neurotransmitters.


METHODS
Cholecystectomy was performed on 39 lean, 19 Lepob, and 20 Lepdb 12-week-old female mice. The gallbladder was divided and enzymatically digested. Half of each gallbladder's myocytes had contraction induced by CCK (10(-8) mol/L, n = 38) or ACh (10(-5) mol/L, n = 40).


RESULTS
Body weights, gallbladder volumes, and serum glucoses were greater for Lep(ob) and Lepdb mice compared to controls (P < .001). Resting myocyte lengths from Lepob and Lepdb mice were 93% and 91% of the length of controls (P < .001). In response to CCK, lean myocytes shortened 6% (P < .01), while myocytes from obese mice demonstrated no shortening. None of the myocytes demonstrated significant shortening with ACh.


CONCLUSIONS
These data suggest that gallbladder myocytes from obese mice are (1) foreshortened and (2) have a diminished response to cholecystokinin. We conclude that altered leptin and/or increased glucose may foreshorten myocytes and decrease response to cholecystokinin.
Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Shannon J
SJ
Graewin
Keun-Ho
KH
Lee
James M
JM
Kiely
Carol L
CL
Svatek
Attila
A
Nakeeb
Henry A
HA
Pitt
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002766:Cholecystokinin / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000503:physiopathology; D005260:Female; D005704:Gallbladder / Q000166:cytology / Q000187:drug effects*; D020738:Leptin / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009765:Obesity
D001786:Blood Glucose; D020738:Leptin; D002766:Cholecystokinin; D000109:Acetylcholine