Nature Reviews Endocrinology

Diabetes mellitus is characterized by the failure of insulin-secreting pancreatic ?-cells (or ?-cell death) due to either autoimmunity (type 1 diabetes mellitus) or failure to compensate for insulin resistance (type 2 diabetes mellitus; T2DM). In addition, mutations of critical genes cause monogenic diabetes. The endoplasmic reticulum (ER) is the primary site for proinsulin folding; therefore, ER proteostasis is crucial for both ?-cell function and survival under physiological and pathophysiological challenges. Importantly, the ER is also the major intracellular Ca2+ storage organelle, generating Ca2+ signals that contribute to insulin secretion. ER stress is associated with the pathogenesis of diabetes mellitus. In this Review, we summarize the mutations in monogenic diabetes that play causal roles in promoting ER stress in ?-cells. Furthermore, we discuss the possible mechanisms responsible for ER proteostasis imbalance with a focus on T2DM, in which both genetics and environment are considered important in promoting ER stress in ?-cells. We also suggest that controlled insulin secretion from ?-cells might reduce the progression of a key aspect of the metabolic syndrome, namely nonalcoholic fatty liver disease. Finally, we evaluate potential therapeutic approaches to treat T2DM, including the optimization and protection of functional ?-cell mass in individuals with T2DM.

خرید پکیج و مشاهده آنلاین مقاله

Brain insulin signalling in metabolic homeostasis and disease

Thomas Scherer, Kenichi Sakamoto & Christoph Buettner

doi : 10.1038/s41574-021-00498-x

Nature Reviews Endocrinology volume 17, pages468–483 (2021)

Insulin signalling in the central nervous system regulates energy homeostasis by controlling metabolism in several organs and by coordinating organ crosstalk. Studies performed in rodents, non-human primates and humans over more than five decades using intracerebroventricular, direct hypothalamic or intranasal application of insulin provide evidence that brain insulin action might reduce food intake and, more importantly, regulates energy homeostasis by orchestrating nutrient partitioning. This Review discusses the metabolic pathways that are under the control of brain insulin action and explains how brain insulin resistance contributes to metabolic disease in obesity, the metabolic syndrome and type 2 diabetes mellitus.

خرید پکیج و مشاهده آنلاین مقاله

Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus

Daniel Ferguson & Brian N. Finck

doi : 10.1038/s41574-021-00507-z

Nature Reviews Endocrinology volume 17, pages484–495 (2021)

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease in the world, yet there are still no approved pharmacological therapies to prevent or treat this condition. NAFLD encompasses a spectrum of severity, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Although NASH is linked to an increased risk of hepatocellular carcinoma and cirrhosis and has now become the leading cause of liver failure-related transplantation, the majority of patients with NASH will ultimately die as a result of complications of type 2 diabetes mellitus (T2DM) and cardiometabolic diseases. Importantly, NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM. Thus, targeting these interconnected conditions and taking a holistic attitude to the treatment of metabolic disease could prove to be a very beneficial approach. This Review will explore the latest relevant literature and discuss the ongoing therapeutic options for NAFLD focused on targeting intermediary metabolism, insulin resistance and T2DM to remedy the global health burden of these diseases.

خرید پکیج و مشاهده آنلاین مقاله

The role of regulated necrosis in endocrine diseases

Wulf Tonnus, Alexia Belavgeni, Felix Beuschlein, Graeme Eisenhofer, Martin Fassnacht, Matthias Kroiss, Nils P. Krone, Martin Reincke, Stefan R. Bornstein & Andreas Linkermann

doi : 10.1038/s41574-021-00499-w

Nature Reviews Endocrinology volume 17, pages497–510 (2021)

The death of endocrine cells is involved in type 1 diabetes mellitus, autoimmunity, adrenopause and hypogonadotropism. Insights from research on basic cell death have revealed that most pathophysiologically important cell death is necrotic in nature, whereas regular metabolism is maintained by apoptosis programmes. Necrosis is defined as cell death by plasma membrane rupture, which allows the release of damage-associated molecular patterns that trigger an immune response referred to as necroinflammation. Regulated necrosis comes in different forms, such as necroptosis, pyroptosis and ferroptosis. In this Perspective, with a focus on the endocrine environment, we introduce these cell death pathways and discuss the specific consequences of regulated necrosis. Given that clinical trials of necrostatins for the treatment of autoimmune conditions have already been initiated, we highlight the therapeutic potential of such novel therapeutic approaches that, in our opinion, should be tested in endocrine disorders in the future.

خرید پکیج و مشاهده آنلاین مقاله

Author Correction: Optoacoustic imaging in endocrinology and metabolism

Angelos Karlas, Miguel A. Pleitez, Juan Aguirre & Vasilis Ntziachristos

doi : 10.1038/s41574-021-00515-z

Nature Reviews Endocrinology volume 17, page511 (2021)

خرید پکیج و مشاهده آنلاین مقاله