Diabetes increases pancreatic fibrosis during chronic inflammation

Abstract

Diabetes and fibrosis can be concurrent processes in several diseases such as cystic fibrosis or chronic pancreatitis. To evaluate whether diabetes can influence fibrosis and thus aggravate the pathological process, the progression of chronic pancreatitis was assessed in diabetic and non diabetic mice. For this purpose, insulin producing beta-cells in C57Bl/6J mice were selectively impaired by administration of streptozotocin. Chronic pancreatitis was then induced by repetitive administration of cerulein in normoglycaemic and hyperglycaemic mice. Diabetes caused enhanced collagen I deposition within three weeks of the onset of chronic pancreatitis and increased the proliferation of interstitial cells. This was accompanied by an increased number of interlobular fibroblasts, which expressed S100A4 (fibroblast-specific protein-1) and stimulation of α-smooth muscle actin expression of pancreatic stellate cells. In addition, the observed aggravation of chronic pancreatitis by diabetes also led to a significantly enhanced atrophy of the pancreas, increased infiltration of inflammatory chloracetate esterase positive cells and enhanced acinar cell death. We conclude that diabetes has a detrimental influence on the progression of chronic pancreatitis by aggravating fibrosis, inflammation and pancreatic atrophy.

Diabetes increases pancreatitis induced systemic inflammation but has little effect on inflammation and cell death in the lung

“…The presented data demonstrate that diabetes during AP (i) enhances IL-6 concentration in blood plasma while decreasing the number of lymphocytes in the blood, (ii) only marginally increases pancreatitis induced lung inflammation, but (iii) does not lead to major cell death or proliferation in the lung epithelium. We conclude that diabetes has a fundamental influence on the progression of pancreatitis at a local level as published previously (Zechner et al 2012(Zechner et al , 2014 and can also increase systemic inflammatory parameters such as IL-6 concentration in blood plasma. However, these data also suggest that the observed strong aggravation of pancreatitis by diabetes leads neither to strong enhancement of lung inflammation nor to induction of cell death in the lung epithelium.…”

“…We conclude that diabetes has a fundamental influence on the progression of pancreatitis at a local level as published previously (Zechner et al . , , ) and can also increase systemic inflammatory parameters such as IL‐6 concentration in blood plasma. However, these data also suggest that the observed strong aggravation of pancreatitis by diabetes leads neither to strong enhancement of lung inflammation nor to induction of cell death in the lung epithelium.…”

“…We have previously demonstrated in experimental settings that diabetes indeed aggravates the local pathophysiological process during acute as well as chronic pancreatitis (Zechner et al . , , ). The purpose of this study was to explore if the aggravation of AP by diabetes leads to increased systemic inflammation, and if adequate alterations in the lung can be observed.…”

Preclinical pharmacokinetic, biodistribution, imaging and therapeutic efficacy of 177Lu-Labeled glycated bombesin analogue for gastrin-releasing peptide receptor-positive prostate tumor targeting

“…In addition, the high uptake of radio-peptides in the pancreas might induce chronic pancreatitis. Because the pancreas has features of both endocrine and exocrine glands, chronic pancreatitis can cause type 2 diabetes via beta celldamage and weight loss due to malabsorption [37,38]. The results (Fig.…”

Analysis of Axin2 expression and function in murine models for pancreatic cancer

“…1a). Since previous publications demonstrated a detrimental influence of streptozotocin (STZ) induced hyperglycemia on the progression of chronic pancreatitis [10], the pancreas of hyperglycemic mice with chronic pancreatitis (STZ+Cer) was compared to the pancreas of normoglycemic mice with chronic pancreatitis (Cer) and hyperglycemic mice, which had no pancreatitis (STZ). A reliable induction of hyperglycemia in STZ treated mice (STZ: 21.5/18.6–25.0, STZ+Cer: 20.3/16.2–23.0) compared to control mice (Cer: 5.7/4.8–6.2; median/interquartile range in mmol/L on day 22) was noticed.…”