Alcohol consumption can trigger inflammation in various organs such as the intestines, liver, lungs, joint, brain and pancreas. The inflammation of pancreas, commonly referred to as pancreatitis, may arise from high or prolonged alcohol consumption, and is a potential risk factor for the development of diabetes, specifically non-insulin dependent diabetes mellites (DM-II). Every year, acute pancreatitis is responsible for 250,000 hospital admissions, which has seen a 20% increase over the last decade. Alcohol consumption may result in the inflammation of pancreas by causing pancreatic secretions to have more viscosity. Aggregation of pancreatic secretions produce protein plugs that result in inflammation, as well as subsequent loss of acinar, islet, and ductal cells. Due to the progressive destruction of pancreatic tissue which may rid the pancreas of insulin-producing beta-islet cells, DM-II may also arise from alcohol-induced inflammation of pancreas. With these premises, it was hypothesized that alcohol consumption enhances the development of pancreatitis and DM-II. QIAGEN Ingenuity Pathway Analysis (IPA) software and CLC Genomics Workbench 22 (CLC 22) were employed for a network meta-analysis on molecular mechanisms underlying alcohol consumption on the inflammation of pancreas, as well as on the onset of DM-II. CLC 22 was used to analyze genomes from a sample size of 87 patients with acute pancreatitis, as well as genomes of 32 healthy patients. Healthy genomes were compared to those with pancreatitis, which identified 36,693 differentially expressed genes (DEG). These 36,693 DEG’s were then uploaded to IPA and compared to the total number of molecules associated with ethanol (EtOH); out of 786 molecules that were found to be associated with EtOH through IPA’s QIAGEN Knowledge Base (QKB), a total of 441 molecules overlapped with the 36,693 DEG’s. These 441 identified common molecules were analyzed through Core Analysis of IPA, which found top 340 enriched canonical pathways that were most associated with the 441 molecules. Upon mimicking EtOH exposure, 156 pathways were upregulated, 57 pathways were downregulated, and 127 did not show any change following EtOH simulation. Upon observing how EtOH modulates several canonical pathways associated with the DEG’s from pancreatitis samples, this study confirmed EtOH’s close modulation to inflammation of pancreas and DM-II through IPA. In a parallel study, IPA’s “Grow” tool was used to find that a total of 786 molecules were associated with EtOH, 1074 molecules were associated with DM-II, and 316 molecules were associated with the inflammation of pancreas. The “Compare” tool was then used to identify molecules that were shared between EtOH, DM-II, and inflammation of pancreas. First, it was found that 56 molecules overlapped between EtOH and inflammation of pancreas. Simulated exposure to EtOH in this 56-molecule network, using the Molecular Activity Predictor (MAP) tool, resulted in the activation of the inflammation of pancreas, with a p-value of 0.044. Secondly, it was found that 128 molecules overlap between EtOH and DM-II. Simulated exposure to EtOH was found to subsequently augment DM-II, with a p-value of 0.016. Thirdly, it was found that 76 molecules overlapped between DM-II and inflammation of pancreas. Simulated exposure of this network to EtOH resulted in the activation of both inflammation of pancreas and DM-II. Simulated EtOH exposure also downregulated the expression of insulin receptor 1&2, and NR3C1 receptors. This combined effect further led to the downregulation of insulin. In addition, MIF expression was decreased. Downregulated insulin and upregulated MIF jointly promoted DM-II. Taken together, our network meta-analysis studies revealed the molecular mechanisms underlying alcohol augmentation of inflammation of the pancreas, possibly leading to the onset and progression of DM-II.
December 28, 2025