Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice

Shannon J. Graewin, Keun Ho Lee, James M. Kiely, Carol L. Svatek, Attila Nakeeb, Henry A. Pitt

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lep ob) and leptin-resistant (Lep db) 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 Lep ob and Lep db obese mice would not respond normally to neurotransmitters. Methods Cholecystectomy was performed on 39 lean, 19 Lep ob, and 20 Lep db 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 Lep db mice compared to controls (P <.001). Resting myocyte lengths from Lep ob and Lep db 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.

Original languageEnglish (US)
Pages (from-to)431-436
Number of pages6
JournalSurgery
Volume136
Issue number2
DOIs
StatePublished - Aug 2004
Externally publishedYes

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Obese Mice
Cholecystokinin
Gallbladder
Muscle Cells
Leptin
Acetylcholine
Glucose
Cholecystectomy
Gallstones
Neurotransmitter Agents
Obesity
Body Weight

ASJC Scopus subject areas

  • Surgery

Cite this

Graewin, S. J., Lee, K. H., Kiely, J. M., Svatek, C. L., Nakeeb, A., & Pitt, H. A. (2004). Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice. Surgery, 136(2), 431-436. https://doi.org/10.1016/j.surg.2004.05.020

Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice. / Graewin, Shannon J.; Lee, Keun Ho; Kiely, James M.; Svatek, Carol L.; Nakeeb, Attila; Pitt, Henry A.

In: Surgery, Vol. 136, No. 2, 08.2004, p. 431-436.

Research output: Contribution to journalArticle

Graewin, SJ, Lee, KH, Kiely, JM, Svatek, CL, Nakeeb, A & Pitt, HA 2004, 'Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice', Surgery, vol. 136, no. 2, pp. 431-436. https://doi.org/10.1016/j.surg.2004.05.020
Graewin, Shannon J. ; Lee, Keun Ho ; Kiely, James M. ; Svatek, Carol L. ; Nakeeb, Attila ; Pitt, Henry A. / Gallbladder myocytes are short and cholecystokinin-resistant in obese diabetic mice. In: Surgery. 2004 ; Vol. 136, No. 2. pp. 431-436.
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N2 - Background Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lep ob) and leptin-resistant (Lep db) 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 Lep ob and Lep db obese mice would not respond normally to neurotransmitters. Methods Cholecystectomy was performed on 39 lean, 19 Lep ob, and 20 Lep db 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 Lep db mice compared to controls (P <.001). Resting myocyte lengths from Lep ob and Lep db 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.

AB - Background Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lep ob) and leptin-resistant (Lep db) 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 Lep ob and Lep db obese mice would not respond normally to neurotransmitters. Methods Cholecystectomy was performed on 39 lean, 19 Lep ob, and 20 Lep db 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 Lep db mice compared to controls (P <.001). Resting myocyte lengths from Lep ob and Lep db 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.

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