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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.

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.

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., …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., …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., …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.

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., …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.

Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism (2018)
Journal Article
Ardestani, A., Lupse, B., & Maedler, K. (2018). Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism. Trends in Endocrinology & Metabolism, 29(7), 492-509. https://doi.org/10.1016/j.tem.2018.04.006

The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathw... Read More about Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism.

An SCFfbxo28 E3 ligase protects pancreatic β-cells from apoptosis (2018)
Journal Article
Gorrepati, K. D. D., He, W., Lupse, B., Yuan, T., Maedler, K., & Ardestani, A. (2018). An SCFfbxo28 E3 ligase protects pancreatic β-cells from apoptosis. International Journal of Molecular Sciences, 19(4), Article 975. https://doi.org/10.3390/ijms19040975

Loss of pancreatic β-cell function and/or mass is a central hallmark of all forms of diabetes but its molecular basis is incompletely understood. β-cell apoptosis contributes to the reduced β-cell mass in diabetes. Therefore, the identification of im... Read More about An SCFfbxo28 E3 ligase protects pancreatic β-cells from apoptosis.

Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response (2018)
Journal Article
Gorrepati, K. D. D., Lupse, B., Annamalai, K., Yuan, T., Maedler, K., & Ardestani, A. (2018). Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response. iScience, 1, 72-86. https://doi.org/10.1016/j.isci.2018.02.003

Impaired pancreatic β-cell survival contributes to the reduced β-cell mass in diabetes, but underlying regulatory mechanisms and key players in this process remain incompletely understood. Here, we identified the deubiquitinase ubiquitin-specific pro... Read More about Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response.

mTORC2 Signaling: A Path for Pancreatic β Cell's Growth and Function (2018)
Journal Article
Yuan, T., Lupse, B., Maedler, K., & Ardestani, A. (2018). mTORC2 Signaling: A Path for Pancreatic β Cell's Growth and Function. Journal of Molecular Biology, 430(7), 904-918. https://doi.org/10.1016/j.jmb.2018.02.013

The mechanistic target of rapamycin (mTOR) signaling pathway is an evolutionary conserved pathway that senses signals from nutrients and growth factors to regulate cell growth, metabolism and survival. mTOR acts in two biochemically and functionally... Read More about mTORC2 Signaling: A Path for Pancreatic β Cell's Growth and Function.