8258 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer

Carlos Viesi; Ian Tamburini; Hosung Bae; Erwin Ilegems; Leandro Velez; Mingqi Zhou; Christy Nguyen; Casey Johnson; Cholsoon Jang; Erika Nishimura; Marcus Seldin

doi:10.1210/jendso/bvae163.793

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8258 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer

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8258 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer

Carlos Viesi, Ian Tamburini, Hosung Bae, Erwin Ilegems, Leandro Velez, Mingqi Zhou, Christy Nguyen, Casey Johnson, Cholsoon Jang, Erika Nishimura, …

Journal of the Endocrine Society, Vol.8(Suppl 1)

10/05/2024

DOI: 10.1210/jendso/bvae163.793

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Abstract

Disclosure: C. Viesi: None. Type 2 Diabetes (T2D) affects over 530 million people around the globe. Insulin resistance, encompassing tissues such as muscle, adipose, and liver, is the initial step hallmarked by hyperinsulinemia. Coupled with β-cell failure, these coordinated responses progress to T2D, becoming irreversible and medically challenging. Despite the well-established requirement for communication between pancreas and peripheral tissues in T2D progression, this area remains almost entirely unexplored. Here, we performed a human population genetic screening across 310 individuals to search for new endocrine regulators of pancreas function. Specifically, global gene expression from 18 peripheral tissues was analyzed to identify potential endocrine regulators of insulin secretion. This analysis prioritized liver-specific Haptoglobin-related protein (HPR) as genetically-enriched with islet insulin responses. Mouse models using AAV technology and acute protein administration of HPR showed that this newly secreted protein is sufficient to prevent diet-induced insulin resistance through enhanced beta-cell respiration. When mice were administered soluble HPR, then pancreatic tissue subjected to global RNA-sequencing, enhanced respiration pathways were observed. Next, we generated hepatocyte-specific overexpression models using AAV, which were sufficient to rescue whole-body glucose disposal profiles and weight gain in diet-induced insulin-resistant mice. Altogether, these findings highlight HPR as a novel soluble protein which signals from liver to pancreatic islets. Presentation: 6/3/2024

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Title: Subtitle: 8258 Haptoglobin-related protein (HPR) new role as insulin secretion enhancer
Creators: Carlos Viesi - University of California, Irvine
Ian Tamburini - University of California, Irvine
Hosung Bae - University of California, Irvine
Erwin Ilegems - Novo Nordisk (Denmark)
Leandro Velez - University of California, Irvine
Mingqi Zhou - University of California, Irvine
Christy Nguyen - University of California, Irvine
Casey Johnson - University of California, Irvine
Cholsoon Jang - University of California, Irvine
Erika Nishimura - Novo Nordisk (Denmark)
Marcus Seldin - University of California, Irvine
Resource Type: Abstract
Publication Details: Journal of the Endocrine Society, Vol.8(Suppl 1)
DOI: 10.1210/jendso/bvae163.793
ISSN: 2472-1972
eISSN: 2472-1972
Publisher: Oxford University Press
Language: English
Date published: 10/05/2024
Academic Unit: Internal Medicine
Record Identifier: 9985217112302771

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