Pancreatic steatosis

Ramkissoon, Resham; Gardner, Timothy B.

doi:10.1097/mog.0000000000000566

Cited by 10 publications

(14 citation statements)

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“…This suggests the Ins1 -/- genetic background may contribute to replacement of parenchyma with fat and the relative lack of ductal metaplasia; however, future studies are needed to examine this hypothesis. In addition, pancreatitis can also induce acinar cell necrosis or apoptosis, which is subsequently replaced by adipocytes [ 48 , 49 ]. HFD-induced obesity can also cause fat accumulation in the exocrine parenchyma [ 48 , 50 ], but we did not observe this extent of fat accumulation with the same diet in our previous mouse model [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, pancreatitis can also induce acinar cell necrosis or apoptosis, which is subsequently replaced by adipocytes [ 48 , 49 ]. HFD-induced obesity can also cause fat accumulation in the exocrine parenchyma [ 48 , 50 ], but we did not observe this extent of fat accumulation with the same diet in our previous mouse model [ 19 ]. Together it seems that the combined effects of Kras-associated inflammation, HFD, and the Ins1 -/- genetic background may have resulted in fat displacing ~ 2/3 of normal pancreatic parenchyma in our PK- Ins1 -/- mouse model.…”

Section: Discussionmentioning

confidence: 99%

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Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

et al. 2022

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Background Hyperinsulinemia is independently associated with increased risk and mortality of pancreatic cancer. We recently reported that genetically reduced insulin production resulted in ~ 50% suppression of pancreatic intraepithelial neoplasia (PanIN) precancerous lesions in mice. However, only female mice remained normoglycemic, and only the gene dosage of the rodent-specific Ins1 alleles was tested in our previous model. Moreover, we did not delve into the molecular and cellular mechanisms associated with modulating hyperinsulinemia. Methods We studied how reduced Ins2 gene dosage affects PanIN lesion development in both male and female Ptf1aCreER;KrasLSL-G12D mice lacking the rodent-specific Ins1 gene (Ins1-/-). We generated control mice having two alleles of the wild-type Ins2 gene (Ptf1aCreER;KrasLSL-G12D;Ins1-/-;Ins2+/+) and experimental mice having one allele of Ins2 gene (Ptf1aCreER;KrasLSL-G12D;Ins1-/-;Ins2+/-). We then performed thorough histopathological analyses and single-cell transcriptomics for both genotypes and sexes. Results High-fat diet–induced hyperinsulinemia was transiently or modestly reduced in female and male mice, respectively, with only one allele of Ins2. This occurred without dramatically affecting glucose tolerance. Genetic reduction of insulin production resulted in mice with a tendency for less PanIN and acinar-to-ductal metaplasia (ADM) lesions. Using single-cell transcriptomics, we found hyperinsulinemia affected multiple cell types in the pancreas, with the most statistically significant effects on local immune cell types that were highly represented in our sampled cell population. Specifically, hyperinsulinemia modulated pathways associated with protein translation, MAPK-ERK signaling, and PI3K-AKT signaling, which were changed in epithelial cells and subsets of immune cells. Conclusions These data suggest a potential role for the immune microenvironment in hyperinsulinemia-driven PanIN development. Together with our previous work, we propose that mild suppression of insulin levels may be useful in preventing pancreatic cancer by acting on multiple cell types.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

et al. 2022

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“…Approximately 30-50% of the pancreas was replaced by adipocytes. Pancreatitis can induce acinar cell necrosis or apoptosis, which is subsequently replaced by adipocytes (49, 50). HFD-induced obesity can also cause fat accumulation in the exocrine parenchyma (49, 51), but we did not observe this extent of fatty replacement with the same diet in our previous model (19).…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatitis can induce acinar cell necrosis or apoptosis, which is subsequently replaced by adipocytes (49, 50). HFD-induced obesity can also cause fat accumulation in the exocrine parenchyma (49, 51), but we did not observe this extent of fatty replacement with the same diet in our previous model (19). Together it seems that the combined effects of Kras-associated inflammation, HFD, and the Ins1 -/- genetic background may have resulted in fat displacing ∼2/3 of normal pancreatic parenchyma in our PK- Ins1 -/- mouse model.…”

Section: Discussionmentioning

confidence: 99%

Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

Zhang

Winter

Wang

et al. 2021

Preprint

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Hyperinsulinemia is independently associated with increased risk and mortality of pancreatic cancer. We recently reported that a ~50% reduction in pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in mice could be achieved with reduced insulin production. However, only female mice remained normoglycemic and only the gene dosage of rodent-specific Ins1 alleles was tested in our previous model. Moreover, we did not delve into the molecular and cellular mechanisms associated with modulating hyperinsulinemia. Here, we studied PanIN lesion development in both male and female Ptf1aCreER;KrasLSL-G12D mice lacking the rodent specific Ins1 gene, and possessing one or two alleles of the wild-type Ins2 gene to modulate insulin production. High-fat diet induced hyperinsulinemia was transiently and modestly reduced, without affecting glucose tolerance, in male and female mice with only one allele of Ins2. Genetic reduction of insulin production resulted in mice with a tendency for less PanIN and acinar-to-ductal metaplasia (ADM) lesions. Using single-cell transcriptomics, we found hyperinsulinemia affected multiple cell types in the pancreas, with the most statistically significant effects on local immune cell populations, which were highly represented in our analysis. Specifically, hyperinsulinemia modulated pathways associated with protein translation, MAPK-ERK signaling, and PI3K-AKT signaling, which were changed in epithelial cells and subsets of immune cells. These data suggest a role for the immune microenvironment in hyperinsulinemia-driven PanIN development. Together with our previous work, we propose that mild suppression of insulin levels may be useful in preventing pancreatic cancer by acting on multiple cell types.

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“…

IntroductionPancreatic steatosis (PS) was first defined by Ogilvie in a cadaver study, with determination of relationships between age and metabolic comorbidities such as atherosclerosis and diabetes, and it became a subject in which interest has not diminished [1][2][3][4]. It has been shown that fat in the pancreas is related to the severity of pancreatitis, pancreatic cancer, and postoperative pancreatic fistula [5][6][7].

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confidence: 99%

The efficacy of the 3-dimensional vibe-caipirinha-dixon technique in the evaluation of pancreatic steatosis

2020

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Background/aim: CAIPIRINHA is a new technique in abdominal imaging. Pancreatic steatosis (PS) is a subject of increasing scientific interest. The aim of this study was to investigate the efficacy of the isotropic 3D-VIBE-CAIPIRINHA -DIXON technique on a new generation 3-tesla MR unit in the evaluation of PS. Materials and methods:In this retrospective study, the imaging findings of 49 patients with PS and 41 control subjects were examined. The pancreas-to-spleen ratio (PSR), pancreas-to-muscle ratio (PMR), and pancreatic signal intensity index (PSII) were defined as 3 new parameters and these indexes were calculated from the in-phase/out of phase 3D-VIBE-CAIPIRINHA-DIXON images. Results:The PSR, PMR, and PSII values were significantly different between the patient and control groups (P = 0.001, P = 0.009, P < 0.001, respectively). Statistically significant differences were observed between patient and control groups for ROI measurements of fatty areas on these sequences/images: subtraction (in-out) (P < 0.001), T2W HASTE (P < 0.001), DIXON-fat (P < 0.001), fat-suppressed T1W (P = 0.002), and subtraction (out-in) (P = 0.010). Conclusion:Evaluation of PS with the 3D-VIBE-CAIPIRINHA-DIXON technique can be made rapidly and effectively.

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Pancreatic steatosis

Cited by 10 publications

References 81 publications

Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics

The efficacy of the 3-dimensional vibe-caipirinha-dixon technique in the evaluation of pancreatic steatosis

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