BIG3 inhibits insulin granule biogenesis and insulin secretion

Li, Hongyu; Wei, Shichao; Cheng, Kenneth K.Y.; Gounko, Natalia V.; Ericksen, Russell; Xu, Aimin; Hong, Wanjin; Han, Weiping

doi:10.1002/embr.201338181

Cited by 25 publications

(51 citation statements)

References 31 publications

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“…BIG3-knockout (BKO) mice exhibit postprandial hyperinsulinemia, hyperglycemia, impaired glucose tolerance, and insulin resistance. Interestingly, glucose-stimulated insulin secretion from BKO islets was increased significantly (24). Although we demonstrated that increased insulin granule biogenesis and accumulation led to the enhanced insulin secretion, it was not clear whether insulin granule exocytotic steps were altered.…”

mentioning

confidence: 71%

“…␤-Cells from BKO and control mice were isolated and cultured as described previously (15,24). For electrophysiology experiments, ␤-cells were infected with AdP2X2-GFP 16 h after plating and recorded 24 h later.…”

Section: Methodsmentioning

confidence: 99%

“…Electron microscopy. Electron microscopy was done as described previously (24). Briefly, islets were dehydrated in an ethanol series and embedded in araldite epoxy resin.…”

Section: Methodsmentioning

confidence: 99%

“…Isolated pancreatic islets were infected with AdP2X2-GFP the next morning after isolation and used for experiments 24 h later. Measurement of glucose-induced insulin secretion from isolated islets was done as described previously (24). Briefly, batches of eight similar-sized islets were placed in a 100-l flow chamber under continuous perifusion (0.25 ml/min) with KrebsRinger-HEPES medium (KRH) (in mM: 130 NaCl, 4.7 KCl, 1.2 KH 2PO4, 1.2 MgSO4, and 2.56 CaCl2, supplemented with 1 mg/ml BSA and buffered with 20 mM HEPES-NaOH to pH 7.4) containing 2.8 mM glucose for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…We reported recently that brefeldin A-inhibited guanine nucleotide exchange protein 3 (BIG3), a large Sec7 domain-containing protein, is a novel negative regulator of insulin granule biogenesis in ␤-cells (24). BIG3-knockout (BKO) mice exhibit postprandial hyperinsulinemia, hyperglycemia, impaired glucose tolerance, and insulin resistance.…”

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confidence: 99%

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Detection of insulin granule exocytosis by an electrophysiology method with high temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice

Liu

Gounko

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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mentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

“…Electron microscopy. Electron microscopy was done as described previously (24). Briefly, islets were dehydrated in an ethanol series and embedded in araldite epoxy resin.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Detection of insulin granule exocytosis by an electrophysiology method with high temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice

Liu

Gounko

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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GPCRs, G Proteins, and Their Impact on β‐cell Function

Kowluru

2020

Comprehensive Physiology

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Glucose-induced (physiological) insulin secretion from the islet β-cell involves interplay between cationic (i.e., changes in intracellular calcium) and metabolic (i.e., generation of hydrophobic and hydrophilic second messengers) events. A large body of evidence affirms support for novel regulation, by G proteins, of specific intracellular signaling events, including actin cytoskeletal remodeling, transport of insulin-containing granules to the plasma membrane for fusion, and secretion of insulin into the circulation. This article highlights the following aspects of GPCR-G protein biology of the islet. First, it overviews our current understanding of the identity of a wide variety of G protein regulators and their modulatory roles in GPCR-G protein-effector coupling, which is requisite for optimal β-cell function under physiological conditions. Second, it describes evidence in support of novel, noncanonical, GPCR-independent mechanisms of activation of G proteins in the islet. Third, it highlights the evidence indicating that abnormalities in G protein function lead to islet β-cell dysregulation and demise under the duress of metabolic stress and diabetes. Fourth, it summarizes observations of potential beneficial effects of GPCR agonists in preventing/halting metabolic defects in the islet β-cell under various pathological conditions (e.g., metabolic stress and inflammation). Lastly, it identifies knowledge gaps and potential avenues for future research in this evolving field of translational islet biology. Published 2020. Compr Physiol 10:453-490, 2020. Didactic Synopsis Major teaching points• A large number of GPCRs are expressed in rodent islets and human islets, and they communicate with trimeric G proteins with high degree of specificity.• In addition to GPCR-mediated regulation, G proteins are activated via noncanonical mechanisms.• Activation of GPCR-G protein modules leads to regulation of specific effector proteins, leading to the generation of appropriate second messengers, which are essential for physiological insulin secretion.• GPCR-G protein signaling pathways also regulate functions of monomeric G proteins, which play essential roles in cytoskeletal remodeling and vesicular fusion and insulin exocytosis.• (In)activation of trimeric and monomeric G proteins is facilitated by highly specific regulatory proteins/factors as well as by specific posttranslational modifications.• Metabolic stress promotes aberrant activation and inappropriate localization of G proteins, leading to cell dysfunction and demise.• Agonists of GPCRs afford protection against β-cell dysfunction observed in in vitro and in vivo models of metabolic stress and diabetes.

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Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise

Verbrugge

Alhusen

Kempin

et al. 2021

J of Cellular Biochemistry

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Exercise improves the insulin sensitivity of glucose uptake in skeletal muscle. Due to that, exercise has become a cornerstone treatment for type 2 diabetes mellitus (T2DM). The mechanisms by which exercise improves skeletal muscle insulin sensitivity are, however, incompletely understood. We conducted a systematic review to identify all genes whose gain or loss of function alters skeletal muscle glucose uptake. We subsequently cross-referenced these genes with recently generated data sets on exercise-induced gene expression and signaling. Our search revealed 176 muscle glucose-uptake genes, meaning that their genetic manipulation altered glucose uptake in skeletal muscle. Notably, exercise regulates the expression or phosphorylation of more than 50% of the glucose-uptake genes or their protein products. This included many genes that previously have not been associated with exercise-induced insulin sensitivity. Interestingly, endurance and resistance exercise triggered some common but mostly unique changes in expression and phosphorylation of glucose-uptake genes or their protein products. Collectively, our work provides a resource of potentially new molecular effectors that play a role in the incompletely understood regulation of muscle insulin sensitivity by exercise.

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BIG3 inhibits insulin granule biogenesis and insulin secretion

Cited by 25 publications

References 31 publications

Detection of insulin granule exocytosis by an electrophysiology method with high temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice

Detection of insulin granule exocytosis by an electrophysiology method with high temporal resolution reveals enlarged insulin granule pool in BIG3-knockout mice

GPCRs, G Proteins, and Their Impact on β‐cell Function

Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise

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