Autoimmunity to tetraspanin-7 in type 1 diabetes

McLaughlin, Kerry A.; Tombs, Melissa A; Christie, Michael R.

doi:10.1007/s00430-020-00674-2

Cited by 15 publications

(15 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mutations in Tspan7 have been associated with X‐linked intellectual disability, 36 and Tspan7 has been implicated in the development of the nervous system and synaptic function 37 . Thus, the role of Tspan7 has been reported primarily in relation to its function in the brain, however, its function in metabolism has also been suggested recently 38–42 . TSPAN7 regulates insulin secretion levels by defining a set‐point for glucose‐stimulated insulin secretion, 39 and TSPAN7 is a target of autoantibodies in type 1 diabetes 40–42 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of metabolic phenotypes and distinctive genes in mice with low‐weight gain

Nemoto,

Kubota,

Ishikura

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

Being overweight exacerbates various metabolic diseases, necessitating the identification of target molecules for obesity control. In the current study, we investigated common physiological features related to metabolism in mice with low weight gain: (1) G protein‐coupled receptor, family C, group 5, member B‐knockout; (2) gastric inhibitory polypeptide receptor‐knockout; and (3) Iroquois‐related homeobox 3‐knockout. Moreover, we explored genes involved in metabolism by analyzing differentially expressed genes (DEGs) between low‐weight gain mice and the respective wild‐type control mice. The common characteristics of the low‐weight gain mice were low inguinal white adipose tissue (iWAT) and liver weight despite similar food intake along with lower blood leptin levels and high energy expenditure. The DEGs of iWAT, epididymal (gonadal) WAT, brown adipose tissue, muscle, liver, hypothalamus, and hippocampus common to these low‐weight gain mice were designated as candidate genes associated with metabolism. One such gene tetraspanin 7 (Tspan7) from the iWAT was validated using knockout and overexpressing mouse models. Mice with low Tspan7 expression gained more weight, while those with high Tspan7 expression gained less weight, confirming the involvement of the Tspan7 gene in weight regulation. Collectively, these findings suggest that the candidate gene list generated in this study contains potential target molecules for obesity regulation. Further validation and additional data from low‐weight gain mice will aid in understanding the molecular mechanisms associated with obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of metabolic phenotypes and distinctive genes in mice with low‐weight gain

Nemoto,

Kubota,

Ishikura

et al. 2023

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…Their enzyme activity has also been linked to the generation of autoantigens in T1D [ 33 , 55 , 56 ]. These enzymes, upon activation, can modify constitutive β-cell proteins such as chromogranin A [ 57 , 58 ], preproinsulin [ 59 ], TSPAN7 [ 60 , 61 ], GAD65 [ 62 , 63 ], and ZnT8 [ 64 ], etc. Thus, the loss of calcium homeostasis during ER stress leads to aberrant post-translational modifications of β-cell proteins.…”

Section: Loss Of Ca ++ Homeostasis As a Mechanism ...mentioning

confidence: 99%

Setting the Stage for Insulin Granule Dysfunction during Type-1-Diabetes: Is ER Stress the Culprit?

et al. 2022

View full text Add to dashboard Cite

Type-1-diabetes (T1D) is a multifactorial disorder with a global incidence of about 8.4 million individuals in 2021. It is primarily classified as an autoimmune disorder, where the pancreatic β-cells are unable to secrete sufficient insulin. This leads to elevated blood glucose levels (hyperglycemia). The development of T1D is an intricate interplay between various risk factors, such as genetic, environmental, and cellular elements. In this review, we focus on the cellular elements, such as ER (endoplasmic reticulum) stress and its consequences for T1D pathogenesis. One of the major repercussions of ER stress is defective protein processing. A well-studied example is that of islet amyloid polypeptide (IAPP), which is known to form cytotoxic amyloid plaques when misfolded. This review discusses the possible association between ER stress, IAPP, and amyloid formation in β-cells and its consequences in T1D. Additionally, ER stress also leads to autoantigen generation. This is driven by the loss of Ca++ ion homeostasis. Imbalanced Ca++ levels lead to abnormal activation of enzymes, causing post-translational modification of β-cell proteins. These modified proteins act as autoantigens and trigger the autoimmune response seen in T1D islets. Several of these autoantigens are also crucial for insulin granule biogenesis, processing, and release. Here, we explore the possible associations between ER stress leading to defects in insulin secretion and ultimately β-cell destruction.

show abstract

“…Der Entwicklung des Typ 1 Diabetes liegt eine zellulär-mediierte Autoimmundestruktion der pankreatischen beta-Zelle zugrunde [ 1 , 2 ]. Die Autoimmunmarker inkludieren Inselzellantikörper, GAD65 Antikörper, Insulin Antikörper, Antikörper gegenüber Tyrosinphosphatase IA‑2 und IA-2beta, sowie Antikörper gegenüber Zinktransporter 8 (ZnT8) und Tetraspanin‑7 [ 1 , 5 , 6 ].…”

unclassified