Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

Butler, A. E.; Galasso, Ryan; Matveyenko, Aleksey V.; Rizza, Robert A.; Dry, Sarah M.; Butler, Peter C.

doi:10.1007/s00125-009-1556-8

Cited by 92 publications

(71 citation statements)

References 13 publications

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“…The PDG compartment was readily detectable throughout the human pancreas, with a 2-fold increase in PDG cell replication in individuals with T2DM compared with ND controls. There was also increased replication of epithelia lining ducts adjacent to PDGs in T2DM, consistent with a prior study that revealed increased duct cell replication in T2DM and in obesity (7). Collectively, these findings are consistent with the concept that PDGs deliver cells to adjacent Figure 6.…”

Section: Discussionsupporting

confidence: 90%

“…A well-recognized risk factor for pancreatitis is delay in passage of exocrine secretions through the ductal tree, for example due to obstruction by an impacted ductal stone or intraductal papillary mucinous neoplasia (IPMN) (5,6). We previously documented an increase in replication in the pancreatic ductal tree in T2DM compared with BMI-matched nondiabetic controls (7). Recently, the pancreatic duct gland (PDG) compartment has been proposed as a pancreatic stem cell niche that expands through increased proliferation in response to induced pancreatic inflammation, purportedly to regenerate pancreatic duct epithelium (8,9).…”

Section: Introductionmentioning

confidence: 99%

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Islet inflammation and ductal proliferation may be linked to increased pancreatitis risk in type 2 diabetes

et al. 2017

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Islet inflammation and ductal proliferation may be linked to increased pancreatitis risk in type 2 diabetes

et al. 2017

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“…The effects of DM and obesity on pancreatic ductal pathology were recently studied by Butler et al (2010), who examined the expression of the neoplastic markers cytokeratin and Ki67 in pancreatic ductal epithelia from 45 human autopsy and nine surgical pathology specimens. In autopsy specimens obtained from obese nondiabetic individuals, pancreatic duct replication was seen to be increased tenfold compared with lean nondiabetics.…”

Section: Proliferation Rates Of Pancreatic Ductal Endothelium In Diabmentioning

confidence: 99%

Diabetes and pancreatic cancer

Cui¹,

Andersen²

2012

Endocrine-Related Cancer

123

102

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Epidemiological studies clearly indicate that the risk of pancreatic cancer (PC) is increased in diabetic patients, but most studies focus on overall diabetes or type 2 diabetes mellitus (T2DM), and there are few studies on the risks of type 1 and type 3c (secondary) diabetes. Possible mechanisms for increased cancer risk in diabetes include cellular proliferative effects of hyperglycemia, hyperinsulinemia, and abnormalities in insulin/IGF receptor pathways. Recently, insulin and insulin secretagogues have been observed to increase the PC risk, while metformin treatment reduces the cancer risk in diabetic subjects. In addition, anticancer drugs used to treat PC may either cause diabetes or worsen coexisting diabetes. T3cDM has emerged as a major subset of diabetes and may have the highest risk of pancreatic carcinoma especially in patients with chronic pancreatitis. T3cDM is also a consequence of PC in at least 30% of patients. Distinguishing T3cDM from the more prevalent T2DM among new-onset diabetic patients can be aided by an assessment of clinical features and confirmed by finding a deficiency in postprandial pancreatic polypeptide release. In conclusion, diabetes and PC have a complex relationship that requires more clinical attention. The risk of developing PC can be reduced by aggressive prevention and treatment of T2DM and obesity and the prompt diagnosis of T3cDM may allow detection of a tumor at a potentially curable stage.

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“…The mechanisms of pancreatitis related with incretin mimetics are uncertain. Some animal studies revealed that sitagliptin increased pancreatic ductal replication, ductal metaplasia and rarely induced pancreatitis in mouse model [12,13].…”

Section: Discussionmentioning

confidence: 99%

Acute pancreatitis and Type 2 Diabetes Mellitus; who is guilty?

Küçükler¹,

Şimşek²,

Bağlıcaklıoğlu³

et al. 2015

Eur Res J

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Many factors play a role in the etiology of acute pancreatitis and its pathogenesis is not fully understood. Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new group of agents for the treatment of Diabetes Mellitus (DM). There are some controversies about specific adverse events such as pancreatitis and hypersensitivity reactions. A 50-year-old morbid obese woman presented with upper abdomen pain after the eating food, nausea and vomiting. She was diagnosed with type 2 diabetes mellitus 7 years ago. Vildagliptin had been added to her treatment six months ago. Abdominal examination revealed epigastric tenderness with guarding. Laboratory data revealed elevated pancreatic enzymes. Abdominal computed tomography (CT) showed features of pancreatitis. Vildagliptin was stopped and patient's symptoms had diminished in parallel with normalization of pancreatic enzymes; and at the 5th day patient was discharged with healthy condition. She was free of symptoms and all laboratory data were normal at the 30th day after discharge. It is important to keep in mind that diabetic patients have an increased risk of pancreatitis which may be related to obesity, hyperlipidemia and/or drugs. Received: 23.03.2015; Accepted: 05.06.2015: Published Online: 04.07.2015 Alcohol and gallstones are the etiology of chronic pancreatitis in many adults. Other etiologic factors are biliary sludge and microlithiasis, smoking, hypertriglyceridemia, hypercalcemia, drugs, obesity, diabetes, infections and toxins, trauma, pancreas divisum, vascular disease, pregnancy and idiopathic [1]. Patients with diabetes mellitus have a 2 fold increase in the risk of pancreatitis due to factors such as obesity, gallstones, elevated triglycerides, and medications [2,3]. Obesity increases risk of pancreatitis and pancreas carcinoma due to increased inflammation [4]. Incretin mimetics, glucagon-like peptide-1 receptor (GLP-1R) agonists and DPP-4 inhibitors are new anti-diabetic agents which can cause pancreatitis as side effect. Postmarketing events of acute pancreatitis have been reported in patients receiving sitagliptin, vildagliptin, or saxagliptin. Most of the cases with pancreatitis are reported with sitagliptin among DPP-4 inhibitors; although there are a few case reports related to vildagliptin, too. In this paper, we report a case of acute pancreatitis which may be associated DPP-4 inhibitors, obesity or DM itself. Case Report ABSTRACT 74

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Pancreatic duct replication is increased with obesity and type 2 diabetes in humans

Cited by 92 publications

References 13 publications

Islet inflammation and ductal proliferation may be linked to increased pancreatitis risk in type 2 diabetes

Islet inflammation and ductal proliferation may be linked to increased pancreatitis risk in type 2 diabetes

Diabetes and pancreatic cancer

Acute pancreatitis and Type 2 Diabetes Mellitus; who is guilty?

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