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A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis (2024)
Journal Article
Watkins, R., Gamo, A., Choi, S. H., Kumar, M., Buckarma, E. L., McCabe, C., Tomlinson, J., Pereya, D., Lupse, B., Geravandi, S., Werneburg, N. W., Wang, C., Starlinger, P., Zhu, S., Li, S., Yu, S., Surakattula, M., Baguley, T., Ardestani, A., Maedler, K., …Smoot, R. (2024). A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis. PNAS Nexus, 3(3), Article pgae096. https://doi.org/10.1093/pnasnexus/pgae096

Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis c... Read More about A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis.

The liver-derived exosomes stimulate insulin gene expression in pancreatic beta cells under condition of insulin resistance (2023)
Journal Article
Mahmoudi-Aznaveh, A., Tavoosidana, G., Najmabadi, H., Azizi, Z., & Ardestani, A. (2023). The liver-derived exosomes stimulate insulin gene expression in pancreatic beta cells under condition of insulin resistance. Frontiers in endocrinology, 14, Article 1303930. https://doi.org/10.3389/fendo.2023.1303930

Introduction: An insufficient functional beta cell mass is a core pathological hallmark of type 2 diabetes (T2D). Despite the availability of several effective pharmaceuticals for diabetes management, there is an urgent need for novel medications to... Read More about The liver-derived exosomes stimulate insulin gene expression in pancreatic beta cells under condition of insulin resistance.

Abnormal acinar–β-cell crosstalk in type 2 diabetes (2023)
Journal Article
Geravandi, S., & Ardestani, A. (2023). Abnormal acinar–β-cell crosstalk in type 2 diabetes. Trends in Endocrinology & Metabolism, 34(11), 685-687. https://doi.org/10.1016/j.tem.2023.08.006

Cellular crosstalk plays a vital role in maintaining pancreas homeostasis. Recently, in Cell Metabolism, Basile et al. demonstrated that aberrant upregulation of acinar-cell-specific pancreatic elastase CELA3B within endocrine islets reduces β-cell v... Read More about Abnormal acinar–β-cell crosstalk in type 2 diabetes.

Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer (2022)
Journal Article
Angelis, V., Johnston, S. R., Ardestani, A., & Maedler, K. (2022). Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer. Frontiers in endocrinology, 13, Article 830097. https://doi.org/10.3389/fendo.2022.830097

A critical decline of functional insulin-producing pancreatic β-cells is the central pathologic element of both type 1 and type 2 diabetes. Mammalian Sterile 20-like kinase 1 (MST1) is a key mediator of β-cell failure and the identification of nerati... Read More about Case Report: Neratinib Therapy Improves Glycemic Control in a Patient With Type 2 Diabetes and Breast Cancer.

MST1 deletion protects β-cells in a mouse model of diabetes (2022)
Journal Article
Ardestani, A., & Maedler, K. (2022). MST1 deletion protects β-cells in a mouse model of diabetes. Nutrition and Diabetes, 12(1), Article 7. https://doi.org/10.1038/s41387-022-00186-3

The pro-apoptotic kinase Mammalian Sterile 20-like kinase 1 (MST1), an integral component of the Hippo pathway, is a key regulator of organ size, stress response, and tissue homeostasis; its aberrant hyperactivation is linked to multiple pathological... Read More about MST1 deletion protects β-cells in a mouse model of diabetes.

How β cells can smell insulin fragments (2022)
Journal Article
Ardestani, A., & Maedler, K. (2022). How β cells can smell insulin fragments. Cell Metabolism, 34(2), 189-191. https://doi.org/10.1016/j.cmet.2022.01.003

In this issue of Cell Metabolism, Cheng et al. identify olfactory receptor Olfr109 in β cells with increased expression in islets from mouse models of obesity and type 1 and type 2 diabetes. Binding of a small insulin fragment to Olfr109 fosters isle... Read More about How β cells can smell insulin fragments.

The Hippo kinase LATS2 impairs pancreatic β-cell survival in diabetes through the mTORC1-autophagy axis (2021)
Journal Article
Yuan, T., Annamalai, K., Naik, S., Lupse, B., Geravandi, S., Pal, A., Dobrowolski, A., Ghawali, J., Ruhlandt, M., Gorrepati, K. D. D., Azizi, Z., Lim, D. S., Maedler, K., & Ardestani, A. (2021). The Hippo kinase LATS2 impairs pancreatic β-cell survival in diabetes through the mTORC1-autophagy axis. Nature communications, 12(1), Article 4928. https://doi.org/10.1038/s41467-021-25145-x

Diabetes results from a decline in functional pancreatic β-cells, but the molecular mechanisms underlying the pathological β-cell failure are poorly understood. Here we report that large-tumor suppressor 2 (LATS2), a core component of the Hippo signa... Read More about The Hippo kinase LATS2 impairs pancreatic β-cell survival in diabetes through the mTORC1-autophagy axis.

Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes (2021)
Journal Article
Lupse, B., Annamalai, K., Ibrahim, H., Kaur, S., Geravandi, S., Sarma, B., Pal, A., Awal, S., Joshi, A., Rafizadeh, S., Madduri, M. K., Khazaei, M., Liu, H., Yuan, T., He, W., Gorrepati, K. D. D., Azizi, Z., Qi, Q., Ye, K., Oberholzer, J., …Ardestani, A. (2021). Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes. Cell reports, 36(5), Article 109490. https://doi.org/10.1016/j.celrep.2021.109490

Pancreatic β-cell failure is the key pathogenic element of the complex metabolic deterioration in type 2 diabetes (T2D); its underlying pathomechanism is still elusive. Here, we identify pleckstrin homology domain leucine-rich repeat protein phosphat... Read More about Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.

SARS-CoV-2 and pancreas: a potential pathological interaction? (2021)
Journal Article
Geravandi, S., Mahmoudi-aznaveh, A., Azizi, Z., Maedler, K., & Ardestani, A. (2021). SARS-CoV-2 and pancreas: a potential pathological interaction?. Trends in Endocrinology & Metabolism, 32(11), 842-845. https://doi.org/10.1016/j.tem.2021.07.004

The widespread extrapulmonary complications of coronavirus disease 2019 (COVID-19) have gained momentum; the pancreas is another major target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we take a closer look into potential... Read More about SARS-CoV-2 and pancreas: a potential pathological interaction?.

LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes (2021)
Journal Article
Sanchez, P. K. M., Khazaei, M., Gatineau, E., Geravandi, S., Lupse, B., Liu, H., Dringen, R., Wojtusciszyn, A., Gilon, P., Maedler, K., & Ardestani, A. (2021). LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes. Biochemical and biophysical research communications, 568, 158-166. https://doi.org/10.1016/j.bbrc.2021.06.065

The lactate dehydrogenase isoform A (LDHA) is a key metabolic enzyme that preferentially catalyzes the conversion of pyruvate to lactate. Whereas LDHA is highly expressed in many tissues, its expression is turned off in the differentiated adult β-cel... Read More about LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.

Hippo STK kinases drive metabolic derangement (2021)
Journal Article
Maedler, K., & Ardestani, A. (2021). Hippo STK kinases drive metabolic derangement. Nature Metabolism, 3(3), 295-296. https://doi.org/10.1038/s42255-021-00370-2

Obesity is associated with mitochondrial dysfunction and chronic metabolic derailment. Cho et al. report that elevated adipose expression of the Hippo kinases STK3 and STK4 (STK3/4) in obesity and type 2 diabetes decreases the mass and oxidative capa... Read More about Hippo STK kinases drive metabolic derangement.

Deathly triangle for pancreatic β-cells: Hippo pathway-MTORC1-autophagy (2021)
Journal Article
Ardestani, A., & Maedler, K. (2021). Deathly triangle for pancreatic β-cells: Hippo pathway-MTORC1-autophagy. Autophagy, 17(12), 4494-4496. https://doi.org/10.1080/15548627.2021.1972404

A progressive decline in the macroautophagic/autophagic flux is a hallmark of pancreatic β-cell failure in type 2 diabetes (T2D) but the responsible intrinsic factors and underlying molecular mechanisms are incompletely understood. A stress-sensitive... Read More about Deathly triangle for pancreatic β-cells: Hippo pathway-MTORC1-autophagy.

STRIPAK Is a Regulatory Hub Initiating Hippo Signaling (2020)
Journal Article
Ardestani, A., & Maedler, K. (2020). STRIPAK Is a Regulatory Hub Initiating Hippo Signaling. Trends in Biochemical Sciences, 45(4), 280-283. https://doi.org/10.1016/j.tibs.2020.01.005

Signaling modules that integrate the diverse extra- and intracellular inputs to the Hippo pathway were previously unknown. By biochemical and molecular interrogation, Chen et al. established a molecular framework, the RhoA-RHPN-NF2/Kibra-STRIPAK axis... Read More about STRIPAK Is a Regulatory Hub Initiating Hippo Signaling.

Loss of TAZ Boosts PPARγ to Cope with Insulin Resistance (2020)
Journal Article
Ardestani, A., & Maedler, K. (2020). Loss of TAZ Boosts PPARγ to Cope with Insulin Resistance. Cell Metabolism, 31(1), 6-8. https://doi.org/10.1016/j.cmet.2019.12.006

In this issue of Cell Metabolism, El Ouarrat et al. identify the Hippo signaling terminal effector TAZ as an endogenous negative regulator of PPARγ, a master transcriptional regulator of lipid metabolism and insulin sensitivity. Selective destruction... Read More about Loss of TAZ Boosts PPARγ to Cope with Insulin Resistance.

Neratinib protects pancreatic beta cells in diabetes (2019)
Journal Article
Ardestani, A., Li, S., Annamalai, K., Lupse, B., Geravandi, S., Dobrowolski, A., Yu, S., Zhu, S., Baguley, T. D., Surakattula, M., Oetjen, J., Hauberg-Lotte, L., Herranz, R., Awal, S., Altenhofen, D., Nguyen-Tran, V., Joseph, S., Schultz, P. G., Chatterjee, A. K., Rogers, N., …Maedler, K. (2019). Neratinib protects pancreatic beta cells in diabetes. Nature communications, 10(1), Article 5015. https://doi.org/10.1038/s41467-019-12880-5

The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The ide... Read More about Neratinib protects pancreatic beta cells in diabetes.

mTORC1 and IRS1: Another Deadly Kiss (2018)
Journal Article
Ardestani, A., & Maedler, K. (2018). mTORC1 and IRS1: Another Deadly Kiss. Trends in Endocrinology & Metabolism, 29(11), 737-739. https://doi.org/10.1016/j.tem.2018.07.003

Mechanistic target of rapamycin complex (mTORC)1 is the major regulator of metabolism at the cellular and organismal level. mTORC1-mediated regulatory feedback loops enable adaptation to nutrient and growth factor availability and metabolic demand. I... Read More about mTORC1 and IRS1: Another Deadly Kiss.