Abstract
Acute pancreatitis (AP) is one of the leading causes of hospital admission, 20% of which could progress to the severe type with extensive acinar cell necrosis. Clinical studies have reported that diabetes is an independent risk factor of the incidence of AP and is associated with higher severity than nondiabetic subjects. However, how diabetes participates in AP progression is not well defined. To investigate this question, wild-type (wt) and diabetic db/db mice at the age of 16 weeks were used in the study. AP was induced in wt recipients by 10 injections of 50 μg/kg caerulein with a 1 h interval. One hour after the last caerulein injection, bone marrow cells (BMC) isolated from wt and db/db mice were injected intraperitoneally into the recipients (1 × 107cells/recipient). The recipients with no BMC injection served as controls. Thirteen hours after BMC injection, serum lipase activity was 1.8- and 1.3-folds higher in mice that received db/db BMC, compared with those with no injection and wt BMC injection, respectively (p ≤ 0.02 for both). By H&E staining, the overall severity score was 14.7 for no cell injection and 16.6 for wt BMC injection and increased to 22.6 for db/db BMC injection (p ≤ 0.002 for both). In particular, mice with db/db BMC injection developed more acinar cell necrosis and vacuolization than the other groups (p ≤ 0.03 for both). When sections were stained with an antibody against myeloperoxidase (MPO), the density of MPO+ cells in pancreatitis was 1.9- and 1.6-folds higher than wt BMC and no BMC injection groups, separately (p ≤ 0.02 for both). Quantified by ELISA, db/db BMC produced more IL-6, GM-CSF, and IL-10 compared with wt BMC (p ≤ 0.04 for all). In conclusion, BMC of db/db mice produced more inflammatory cytokines. In response to acinar cell injury, diabetic BMC aggravated the inflammation cascade and acinar cell injury, leading to the progression of acute pancreatitis.
Highlights
Type 2 diabetes mellitus (T2DM) accounted for more than 90% among diabetic patients, which is featured as insulin resistance in peripheral organs and insufficient insulin production by dysfunctional pancreatic β cells [1]
The main findings of the study include the following: (1) at the age of 16 weeks, diabetic db/db mice developed hyperglycemia and an increased amount of granulocytes and monocytes in the peripheral blood; (2) bone marrow cells (BMC) of db/db mice produced more granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-10 than that of wt controls; and (3) compared with no cell injection, injection of BMC isolated from db/db mice accelerated inflammation and acinar cell damage in mice with acute pancreatitis (AP) whereas injection of wt BMC did not aggravate disease progression
The second wave comes from infiltrating granulocytes and monocytes that elevate proinflammatory cytokine and chemokine production
Summary
In a meta-analysis involving 698,782 T2DM patients, the hazard ratio was 2.00 (95% CI, 1.83-2.19) for coronary heart disease, 2.27 (95% CI, 1.95-2.65) for ischemic stroke, and. 1.73 (95% CI, 1.51-1.98) for other vascular diseases, respectively, compared with nondiabetic subjects [2]. Apart from vascular complications described above, acute pancreatitis (AP) occurs more frequently in diabetic patients than nondiabetic ones [3, 4]. In a prospective study (n = 547,554), the adjusted hazard ratio of having acute pancreatitis was 1.53 (95% CI, 1.49-1.58) for diabetic patients after 8 years of follow-up. The presence of diabetes was associated with a 1.46-fold increased risk of severe AP compared with nondiabetic ones [3]. A metaanalysis of 354,880 patients revealed that the risk of having AP was 1.55 (95% CI, 1.27-1.90) for diabetic patients
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