| Authors |
Li W, Sasse KC, Bayguinov Y, Ward SM, Perrino BA
|
| Submitted By |
Brian Perrino on 7/30/2018 |
| Status |
Published |
| Journal |
Journal of diabetes research |
| Year |
2018 |
| Date Published |
|
| Volume : Pages |
2018 : 8743874 |
| PubMed Reference |
29955616 |
| Abstract |
Ingested food is received, mixed, and ground into chyme by distinct gastric
motility patterns. Diabetes impairs gastric muscle function, but the mechanisms
underlying diabetes-induced gastric muscle dysfunction are unknown. Here, we
compared the expression and phosphorylation of Ca2+ sensitization and
contractile proteins in human gastric muscles from obese nondiabetic and
diabetic patients. We also compared the spontaneous phasic contractions and the
contractile responses evoked by electrical field stimulation of cholinergic
motor neurons. Fundus and antrum muscles were obtained from sleeve gastrectomies
and were used in in vitro myobath contractile studies and for capillary
electrophoresis and immunodetection of ?-actin, CPI-17, pT38-CPI-17, MYPT1,
pT853-MYPT1, pT696-MYPT1, myosin light chain (MYL9), pS19-MYL9, myosin light
chain kinase (MYLK), protein phosphatase-1d (PP1d), and Rho-associated kinase
(ROCK2). In diabetic fundus muscles, MYLK, ROCK2, and PP1d expression was
unchanged; MYPT1 and CPI-17 expression was decreased; and the pT853/MYPT1 and
pT38/CPI-17 ratios, but not the pT696/MYPT1 ratio, were increased. Although MYL9
expression was increased, the pS19/MYL9 ratio was unchanged in diabetic fundus
muscles. In diabetic antrum muscles, MYLK and MYL9 expression was unchanged, but
ROCK2, CPI-17, and PP1d expression was decreased. The pT38/CPI-17 ratio was
unchanged, while the pS19/MYL9, pT853/MYPT1, and pT696/MYPT1 ratios were
decreased, consistent with the reduced ROCK2 expression. The frequencies of
spontaneous phasic contractions from nondiabetic and diabetic gastric fundus and
antrum muscles did not significantly differ from each other, regardless of age,
sex, or diabetic status. The fold increases in the contractions of diabetic
fundus and antrum muscles in response to increased frequencies of electrical
field stimulation were significantly lower compared to nondiabetic fundus and
antrum muscles. The altered contractile responses and the protein expression and
phosphorylation in gastric muscles of obese patients with diabetes illustrate
the importance of understanding how smooth muscle Ca2+ sensitization mechanisms
contribute to gastric motility.
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