The seventh nationwide epidemiological survey for chronic pancreatitis in Japan: Clinical significance of smoking habit in Japanese patients

Risk factors for diabetes mellitus in chronic pancreatitis: A cohort of 2,011 patients

“…[3][4][5][6][7][8] In the present study, 28% of patients with CP developed DM, which is comparable with previous studies. Our study is consistent with previous studies in risk factors such as alcoholism 3,4 and distal pancreatectomy.…”

“…1,2 Decrease in beta cells and insulin resistance contributes to diabetes mellitus (DM), which accounts for 26% to 41% in the natural course of CP. [3][4][5][6][7][8] The micro-or macrovascular damage secondary to DM is a major threat for CP patients, increasing the mortality. 9,10 Referred to as brittle diabetes, DM secondary to CP (type 3c DM) is characterized by frequent episodes of hypoglycemia, which is difficult to control and affects quality of life of patients with CP.…”

Smoking induced pancreatitis and pancreatic cancer

“…Analysis of the Kras mutations revealed that the presence of the KRAS G12C mutation had 96% specificity and positive predictive value for lung adenocarcinoma, whereas G12R was 99% specific for pancreatic cancer with a positive predictive value of 86% (57). However, it is worth nothing that although Kras mutation is not significantly induced by smoking in the pancreas, recent data indicate that nicotine further stimulates mutated Kras activation leading to more aggressive pancreatic tumors in animal models of the disease (50). The cell signaling mechanism mediating this effect will be discussed in the subsequent section of this review.…”

“…Nicotine induced dedifferentiation of acinar cells by activating the Akt-Erk-Myc signaling; this leads to the inhibition of Gata6 promoter activity, loss of GATA6 protein, and subsequent loss of acinar differentiation and hyper-activation of oncogenic Kras (50).…”

“…Nicotine induced pancreatic cells to acquire gene expression patterns and functional characteristics of cancer stem cells. These effects were markedly attenuated in KPC mice given metformin, which prevented nicotine-induced pancreatic carcinogenesis and tumor growth by up-regulating GATA6 and promoting differentiation toward an acinar cell program (50). Gata6 ablation renders acinar cells more sensitive to the Kras mutation in a mouse model of pancreatic cancer thereby accelerating tumor development.…”