Cover Story Current Issue

White adipose tissue (WAT) is a complex organ that plays a central role in systemic energy balance through its interrelated metabolic, endocrine, and immune functions. Adipocytes, the parenchymal cells of adipose tissue, have diverse functions that include storage and mobilization of lipids. They also release endocrine signals that report energy status to the brain, regulating metabolic functions in peripheral organs. Importantly, the metabolic character of white adipocytes is flexible, with cells capable of assuming distinct anabolic and catabolic/thermogenic phenotypes, often within the same adipose tissue depot

Elizabeth A. Rondini, Vanesa D. Ramseyer, Rayanne B. Burl, Roger Pique-Regi, James G. Granneman

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Current Issue

MTORC1 inhibition drives crinophagic degradation of glucagon

Sangam Rajak, Sherwin Xie, Archana Tewari, Sana Raza, ... Rohit A. Sinha

Objective

Crinophagy is a secretory granule-specific autophagic process that regulates hormone content and secretion in endocrine cells. However, despite being one of the earliest described autophagic processes, its mechanism of action and regulation in mammalian cells remains unclear.

Methods and results

Here, we examined mammalian crinophagy and its modulation that regulate hormone secretion in a glucagon-producing mouse pancreatic α-cell line, alpha TC1 clone 9 (αTC9), and in vivoWestern blotelectron microscopy, and immunofluorescence analyses were performed to study crinophagy and glucagonsecretion in αTC9 cells and C57BL/6 mice, in response to the mammalian target of rapamycin complex 1 (MTORC1) inhibitor rapamycin. Amino acid depletion and pharmacological inhibition of MTORC1 increased the shuttling of glucagon-containing secretory granules into lysosomes for crinophagic degradation to reduce glucagon secretion through a macroautophagy-independent mechanism. Furthermore, MTORC1 inhibition reduced both intracellular and secreted glucagon in rapamycin-treated mice, in response to hypoglycaemia.

Conclusion

In summary, we have identified a novel crinophagic mechanism of intracellular glucagon turnover in pancreatic α-cells regulated by MTORC1 signalling.

 

MTORC1 inhibition drives crinophagic degradation of glucagon

Sangam Rajak, Sherwin Xie, Archana Tewari, Sana Raza, ... Rohit A. Sinha

Objective

Crinophagy is a secretory granule-specific autophagic process that regulates hormone content and secretion in endocrine cells. However, despite being one of the earliest described autophagic processes, its mechanism of action and regulation in mammalian cells remains unclear.

Methods and results

Here, we examined mammalian crinophagy and its modulation that regulate hormone secretion in a glucagon-producing mouse pancreatic α-cell line, alpha TC1 clone 9 (αTC9), and in vivoWestern blotelectron microscopy, and immunofluorescence analyses were performed to study crinophagy and glucagonsecretion in αTC9 cells and C57BL/6 mice, in response to the mammalian target of rapamycin complex 1 (MTORC1) inhibitor rapamycin. Amino acid depletion and pharmacological inhibition of MTORC1 increased the shuttling of glucagon-containing secretory granules into lysosomes for crinophagic degradation to reduce glucagon secretion through a macroautophagy-independent mechanism. Furthermore, MTORC1 inhibition reduced both intracellular and secreted glucagon in rapamycin-treated mice, in response to hypoglycaemia.

Conclusion

In summary, we have identified a novel crinophagic mechanism of intracellular glucagon turnover in pancreatic α-cells regulated by MTORC1 signalling.

 

2020 impact factor: 7.4

The 60 Second Metabolist

In this section authors briefly report on their work recently published in Molecular Metabolism.

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