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2017 ; 14
(4
): 2831-2838
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Pancreatic islet regeneration through PDX-1/Notch-1/Ngn3 signaling after gastric
bypass surgery in db/db mice
#MMPMID28966671
Huang T
; Fu J
; Zhang Z
; Zhang Y
; Liang Y
; Ge C
; Qin X
Exp Ther Med
2017[Oct]; 14
(4
): 2831-2838
PMID28966671
show ga
In view of the compelling anti-diabetic effects of gastric bypass surgery (GBS)
in the treatment of morbid obesity, it is important to clarify its enhancing
effect on pancreatic islets, which is closely linked with diabetes remission in
obese patients, as well as the underlying mechanisms. The present study evaluated
the effects of GBS on glycemic control and other pancreatic changes in db/db
mice. The db/db mice were divided into Control, Sham and GBS group. A significant
improvement in fasting plasma glucose levels and glucose intolerance were
observed post-surgery. At 4 weeks after surgery, further noteworthy changes were
observed in the GBS group, including improved islet structure (revealed by
immunohistochemical analysis), enhanced insulin secretion, pancreatic hyperplasia
and a marked increase in the ratio of ?-cells to non-? endocrine cells.
Furthermore, notable changes in the levels of Notch-1, pancreatic and duodenal
homeobox 1 (PDX-1) and neurogenin 3 (Ngn3) were observed in the GBS group,
indicating a potential role of Notch signaling in pancreatic islet regeneration
after surgery. In addition, results obtained in PDX-1 knockout (KO), Notch-1 KO
and Ngn3 KO mouse models with GBS suggested that elevated PDX-1 resulted in the
inhibition of Notch-1, further facilitated Ngn3 and thus promoted pancreatic
?-cell regeneration after GBS. The present findings demonstrated that GBS in
db/db mice resulted in pancreatic islet regeneration through the
PDX-1/Notch-1/Ngn3 signaling pathway, which also reflected the important role of
the gastrointestinal system in metabolism control.