Glucose metabolism during tumorigenesis in the genetic mouse model of pancreatic cancer.

Authors:
Valentina Pasquale
Valentina Pasquale
Department of Neuroscience and Brain Technologies
Erica Dugnani
Erica Dugnani
San Raffaele Diabetes Research Institute (HSR-DRI)
Italy
Daniela Liberati
Daniela Liberati
Diabetes Research Institute
Paolo Marra
Paolo Marra
San Raffaele Scientific Institute
Antonio Citro
Antonio Citro
San Raffaele Scientific Institute
Italy
Tamara Canu
Tamara Canu
San Raffaele Scientific Institute

Acta Diabetol 2019 Apr 15. Epub 2019 Apr 15.

Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Aim: More than 40% of pancreatic ductal adenocarcinoma (PDAC) patients have glucose intolerance or diabetes. The association has led to two hypotheses: PDAC causes diabetes or diabetes shares risk factors for the development of PDAC. In order to elucidate the relationship between diabetes and PDAC, we investigated the glucose metabolism during tumorigenesis in the LSL-Kras; LSL-Trp53; and Pdx-1-Cre (KPC) mouse, a genetically engineered model of PDAC.

Methods: Male and female KPCs have been fed with standard diet (SD) or high-fat diet (HFD). The imaging-based 4-class tumor staging was used to follow pancreatic cancer development. Not fasting glycemia, 4-h fasting glycemia, insulin, C-peptide, glucose tolerance after OGTT and abdominal fat volume were measured during tumorigenesis.

Results: PDAC development did not lead to an overt diabetic phenotype or to any alterations in glucose tolerance in KPC fed with SD. Consumption of HFD induced higher body weight/abdominal fat volume and worsened glucose homeostasis both in control CRE mice and only in early tumorigenesis stages of the KPC mice, excluding that the cancer development itself acts as a trigger for the onset of dysmetabolic features.

Conclusion: Our data demonstrate that carcinogenesis in KPC mice is not associated with paraneoplastic diabetes.

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Source
http://link.springer.com/10.1007/s00592-019-01335-4
Publisher Site
http://dx.doi.org/10.1007/s00592-019-01335-4DOI Listing
April 2019
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References

(Supplied by CrossRef)
Article in N Engl J Med
M Hidalgo et al.
N Engl J Med 2010
Article in Int J Cancer
B Zhou et al.
Int J Cancer 2017
Article in Clin Gastroenterol Hepatol
AL Lucas et al.
Clin Gastroenterol Hepatol 2016
Article in Acta Diabetol
M Wei et al.
Acta Diabetol 2017
Article in Acta Diabetol
WS Yang et al.
Acta Diabetol 2017
Article in Acta Diabetol
G Balzano et al.
Acta Diabetol 2014
Article in Pancreatology
E Dugnani et al.
Pancreatology 2016
Article in Gastroenterology
R Pannala et al.
Gastroenterology 2008
Article in Nat Rev Gastroenterol Hepatol
RP Sah et al.
Nat Rev Gastroenterol Hepatol 2013
Article in Gastroenterology
ST Chari et al.
Gastroenterology 2005
Article in Gastroenterology.
G Aggarwal et al.
Gastroenterology. 2012

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