Pancreatic exocrine function in patients with diabetes

Larger, Étienne; Philippe, M.F.; Barbot-Trystram, Laurence; Radu, A.; Rotariu, M.; Nobécourt, Estelle; Boîtard, Christian

doi:10.1111/j.1464-5491.2012.03597.x

Cited by 81 publications

(87 citation statements)

References 30 publications

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“…An area of unresolved interest is why pancreata in long standing T1D are decreased in volume and mass in comparison to nondiabetic controls (37). Consistent with that data, exocrine function is also impaired in T1D (38). Hypotheses that have been put forward to account for these findings include loss of the growth promoting properties of insulin and subclinical pancreatitis (19).…”

Section: Discussionsupporting

confidence: 50%

Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes

Moin

Butler

2016

The Journal of Clinical Endocrinology & Metabolism

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Context: Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing beta-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown. Objective: To investigate the pancreatic duct gland (PDG) compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of beta-cells. Design, Setting and Participants: Pancreas from 46 brain dead organ donors (22 with T1D, 24 nondiabetic controls) were investigated for activation (increased proliferation) and markers of pancreatic exocrine and endocrine progenitors. Results: PDG cell replication was increased in T1D (6.3 ± 1.6 vs. 0.6 ± 0.1%, p < 0.001, T1D vs. ND), most prominently in association with pancreatic inflammation. There were increased progenitor-like cells in PDGs of T1D, but predominantly with an exocrine fate. Conclusion:The PDG compartment is activated in T1D consistent with a response to ongoing inflammation, and via resulting ductal hyperplasia may contribute to local obstructive pancreatitis and eventual pancreatic atrophy characteristic of T1D. However, there is no evidence of effective endocrine cell formation from PDGs.PRECIS: PDGs serve as a stem cell niche in the pancreas. Replication in PDGs is increased in T1D, implying ongoing inflammation, but the majority of cells in PDGs have an exocrine rather than endocrine fate. Abbreviations:ChrgA, Chromogranin A. T1D, type 1 diabetes. ND, nondiabetic. PDGs, pancreatic duct glands. INTRODUCTIONIn longstanding type 1 diabetes (T1D), there is a near complete loss of pancreatic beta-cells through autoimmune mediated cell death (1, 2). However, several lines of evidence suggest that there may be ongoing attempted beta-cell regeneration, although insufficient to be clinically meaningful. For example, even in individuals with longstanding T1D, there are still detectable insulin-expressing cells, often isolated and scattered in the exocrine pancreas or in small clusters in and around pancreatic ducts (3,4). Consistent with this, by use of sensitive assays, residual insulin secretion is often present in individuals with longstanding T1D (5-8). The Journal of Clinical Endocrinology & Metabolism; Copyright 2016 DOI: 10.1210/jc.2016 Theoretically, these observations may indicate that there are small populations of beta-cells that elude immune detection or that there is ongoing new beta-cell formation subject to continued autoimmune destruction. In favor of the latter explanation, auto-reactive T-cells targeted to pancreatic beta-cells are frequently detected many years after diabetes onset, implying sustained auto-reactivity (9). In pancreas of individuals with T1D who have sufficient residual beta-cells to evaluate, we previously reported immune cells in close proximity to insulin-expressing cells and an increased frequency of b...

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Section: Discussionsupporting

confidence: 50%

Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes

Moin

Butler

2016

The Journal of Clinical Endocrinology & Metabolism

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“…litus patients have been reported to show a high prevalence of exocrine pancreatic insufficiency (22,23). Compared with diabetes mellitus patients, healthy individuals have a higher ␣-amylase level in the serum and a lower blood glucose level.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic α-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-specific Binding, Endocytosis, and Degradation

Date

Satoh

Iida

et al. 2015

Journal of Biological Chemistry

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Background: Secreted pancreatic ␣-amylase binds to N-glycans of the duodenal brush-border membrane (BBM) and inhibits glucose uptake by SGLT1 at high doses. Results: Enterocytes endocytosed and degraded the ␣-amylase in lysosomes about 30 min after BBM binding. Conclusion: N-Glycan recognition and subsequent internalization of ␣-amylase suppressed and then gradually allowed duodenal glucose absorption. Significance: A newly revealed mechanism regulates postprandial intestinal glucose uptake.

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“…Tanaka et al reported that the CXCL10 and CXCR3, the receptors for CXCL10, activation circuit represents a unique mechanism of rapid beta-cell destruction in FT1DM (3). The possible causes of exocrine failure in patients with diabetes include an autoimmune process associated with type 1 diabetes, a direct trophic effect of insulin on the exocrine pancreas, microangiopathy and atherosclerosis (8). An investigation of the pancreatic exocrine function in a large cohort of patients with diabetes showed the primary factor associated with pancreatic exocrine failure in patients with typical autoimmune type 1 diabetes to be the duration of diabetes (8).…”

Section: Discussionmentioning

confidence: 99%

“…The possible causes of exocrine failure in patients with diabetes include an autoimmune process associated with type 1 diabetes, a direct trophic effect of insulin on the exocrine pancreas, microangiopathy and atherosclerosis (8). An investigation of the pancreatic exocrine function in a large cohort of patients with diabetes showed the primary factor associated with pancreatic exocrine failure in patients with typical autoimmune type 1 diabetes to be the duration of diabetes (8). This observation suggests that the mechanisms underlying exocrine failure in FT1DM patients are different from those underlying exocrine failure in patients with autoimmune type 1 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Recovery from Exocrine Pancreatic Insufficiency in a Patient with Fulminant Type 1 Diabetes

Koyano

Matsumoto

2013

Intern. Med.

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A 34-year-old man was admitted to our hospital with diabetic ketoacidosis due to fulminant type 1 diabetes. The patient's pancreatic exocrine and endocrine functions were as follows: the bentiromide (PABA) test value on day 14 was 33.9%, thus indicating exocrine dysfunction. One year and a half later, the PABA test value had improved to 71.0%. On the other hand, the serum C-peptide level after meal ingestion was under the detection limit. The mechanisms underlying pancreatic exocrine abnormalities seem to be different from those underlying accelerated pancreatic beta-cell failure in patients with fulminant type 1 diabetes.

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Pancreatic exocrine function in patients with diabetes

Cited by 81 publications

References 30 publications

Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes

Increased Proliferation of the Pancreatic Duct Gland Compartment in Type 1 Diabetes

Pancreatic α-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-specific Binding, Endocytosis, and Degradation

Recovery from Exocrine Pancreatic Insufficiency in a Patient with Fulminant Type 1 Diabetes

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