Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Cell Metab. 2023 Oct 26:S1550-4131(23)00372-8. doi: 10.1016/j.cmet.2023.10.003. Online ahead of print.ABSTRACTThe rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that ins...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Anni M Y Zhang Yi Han Xia Jeffrey S H Lin Ken H Chu Wei Chuan K Wang Titine J J Ruiter Jenny C C Yang Nan Chen Justin Chhuor Shilpa Patil Haoning Howard Cen Elizabeth J Rideout Vincent R Richard David F Schaeffer Rene P Zahedi Christoph H Borchers James D Source Type: research
The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Cell Metab. 2023 Oct 20:S1550-4131(23)00377-7. doi: 10.1016/j.cmet.2023.10.008. Online ahead of print.ABSTRACTThe PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty ...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Panu K Luukkonen Kimmo Porthan Noora Ahlholm Fredrik Rosqvist Sylvie Dufour Xian-Man Zhang Tiina E Lehtim äki Wenla Sepp änen Marju Orho-Melander Leanne Hodson Kitt Falk Petersen Gerald I Shulman Hannele Yki-J ärvinen Source Type: research
Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Cell Metab. 2023 Oct 26:S1550-4131(23)00372-8. doi: 10.1016/j.cmet.2023.10.003. Online ahead of print.ABSTRACTThe rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that ins...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Anni M Y Zhang Yi Han Xia Jeffrey S H Lin Ken H Chu Wei Chuan K Wang Titine J J Ruiter Jenny C C Yang Nan Chen Justin Chhuor Shilpa Patil Haoning Howard Cen Elizabeth J Rideout Vincent R Richard David F Schaeffer Rene P Zahedi Christoph H Borchers James D Source Type: research
The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
Cell Metab. 2023 Oct 20:S1550-4131(23)00377-7. doi: 10.1016/j.cmet.2023.10.008. Online ahead of print.ABSTRACTThe PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma β-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty ...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Panu K Luukkonen Kimmo Porthan Noora Ahlholm Fredrik Rosqvist Sylvie Dufour Xian-Man Zhang Tiina E Lehtim äki Wenla Sepp änen Marju Orho-Melander Leanne Hodson Kitt Falk Petersen Gerald I Shulman Hannele Yki-J ärvinen Source Type: research
Hyperinsulinemia acts via acinar insulin receptors to initiate pancreatic cancer by increasing digestive enzyme production and inflammation
Cell Metab. 2023 Oct 26:S1550-4131(23)00372-8. doi: 10.1016/j.cmet.2023.10.003. Online ahead of print.ABSTRACTThe rising pancreatic cancer incidence due to obesity and type 2 diabetes is closely tied to hyperinsulinemia, an independent cancer risk factor. Previous studies demonstrated reducing insulin production suppressed pancreatic intraepithelial neoplasia (PanIN) pre-cancerous lesions in Kras-mutant mice. However, the pathophysiological and molecular mechanisms remained unknown, and in particular it was unclear whether hyperinsulinemia affected PanIN precursor cells directly or indirectly. Here, we demonstrate that ins...
Source: Cell Metabolism - November 1, 2023 Category: Cytology Authors: Anni M Y Zhang Yi Han Xia Jeffrey S H Lin Ken H Chu Wei Chuan K Wang Titine J J Ruiter Jenny C C Yang Nan Chen Justin Chhuor Shilpa Patil Haoning Howard Cen Elizabeth J Rideout Vincent R Richard David F Schaeffer Rene P Zahedi Christoph H Borchers James D Source Type: research
