Mechanisms of Post-Pancreatitis Diabetes Mellitus and Cystic Fibrosis-Related Diabetes: A Review of Preclinical Studies

Abstract

Anatomical proximity and functional correlations between the exocrine and endocrine pancreas warrant reciprocal effects between the two parts. Inflammatory diseases of the exocrine pancreas, such as acute or chronic pancreatitis, or the presence of cystic fibrosis disrupt endocrine function, resulting in diabetes of the exocrine pancreas. Although novel mechanisms are being increasingly identified, the intra- and intercellular pathways regulating exocrine–endocrine interactions are still not fully understood, making the development of new and more effective therapies difficult. Therefore, this review sought to accumulate current knowledge regarding the pathogenesis of diabetes in acute and chronic pancreatitis, as well as cystic fibrosis.

Non-Alcoholic Fatty Liver Disease (NAFLD) Is an Independent Risk Factor for Developing New-Onset Diabetes After Acute Pancreatitis: A Multicenter Retrospective Cohort Study in Chinese Population

“…The effect of exocrine pancreas on endocrine function under physiological conditions can be reflected in the inhibitory effect of amylase and lipase on insulin secretion. One possible explanation is a regulatory mechanism that acts against insulin overproduction and keeps it at a normal level and further avoids exhaustion of β cells ( 11 ). In addition to the regulation of insulin secretion, trypsin may also be involved in islet formation and differentiation ( 29 ).…”

“…A recently published systematic review and meta-analysis by our workgroup reported that new-onset diabetes occurred in 23% of patients with AP ( 9 ), in line with previous research conducted by Das et al ( 10 ). However, other studies provided inconsistent prevalence rates ( 11 ). In particular, few studies provide insight into the frequency of PPDM-A in Chinese patients ( 12 ).…”

“…In addition, the risk factors associated with PPDM-A progression also remain controversial. Some features including the severity of pancreatitis, etiology, the extent of necrosis, presence of infection and other metabolic indicators were considered to be related with the development of diabetes in some of previous research but made no sense in other studies ( 11 ). More evidence is needed to verify these contradictory results and help improving optimal management strategies of this special type of diabetes.…”

miRNAs provide mechanisms for integrated control of endocrine pancreas homeostasis and metabolic disease pathogenesis: a narrative review

“…Post-pancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis, as hyperinsulinemia during pancreatitis might be responsible for the development of insulin resistance (IR) (153). Acute pancreatitis is an acute abdominal inflammatory disease associated with necrosis of the pancreas, systemic inflammation, multiple organ dysfunction, and mechanistically related to a cytosolic calcium overload (154) whereas chronic pancreatitis is a progressive syndrome characterised by pancreatic inflammation, leading to extensive tissue fibrosis and deficiency of pancreatic exocrine and endocrine function (155).…”

Regulatory mechanisms of microRNAs in endocrine disorders and their therapeutic potential

“…Pancreatic inflammatory diseases, including acute or chronic pancreatitis, could result in diabetes ( Gál et al, 2021 ). Pancreatic inflammation has been found to be promoted by the overexpression of miR-29 in β cells of βTG mice ( Sun et al, 2021 ).…”