Zinc supplementation appears to affect the early insulin response to glucose differentially by rs13266634 genotype and could be beneficial for diabetes prevention and/or treatment for some individuals based on SLC30A8 variation.
In the present study, we examined the association between variants in fat mass- and obesity-associated [rs9939609 (A/T)], melanocortin 4 receptor [rs17782313 (C/T), and rs12970134 (A/G)], SLC30A8 [rs13266634 (C/T)], and a member of the potassium voltage-gated channels [rs2237892(C/T)] genes in diabetes patients from Saudi Arabia.
A total of 97 subjects with diabetes onset before age 25, a random C-peptide ≥0.1 ng/mL, and negative for all diabetes autoantibodies (GADA, IA-2, ZnT8, and IAA) were enrolled, after excluding 21 subjects with secondary diabetes or refusal to participate.
Children, younger than 15 years of age (n = 723) who were newly diagnosed with diabetes, were analyzed for ZnT8A, other diabetes-associated autoantibodies, HLA DR-DQ alleles, and metabolic status, which was monitored by pH, plasma glucose, and occurrence of ketoacidosis at diagnosis and through follow-up of C-peptide concentrations, exogenous insulin dose, and glycosylated hemoglobin for 2 years after the diagnosis.
A total of 31 Somali children ≤19 yr were treated for type 1 diabetes (T1D) at the University of Minnesota Masonic Children's Hospital and Children's Hospitals and Clinics of Minnesota underwent analysis of human leukocyte antigen (HLA) alleles (n = 30) and diabetes autoantibodies [glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8); n = 31].
In the present review, we summarize the literature about clinical aspects of ZnT8 in the pathogenesis of diabetes, and suggest that ZnT8 might play a different role between type 1 diabetes mellitus and type 2 diabetes mellitus.
Here, we review the regulation and roles of Zn<sup>2+</sup> ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions.
Leptin (LEP), a protein that plays a fundamental role in the metabolism of energy reserves, and the solute carrier family 30 A8 zinc transporter (SLC30A8) have been consistently associated with diabetes.
The majority of multiple-autoAb<sup>+</sup> individuals progress to diabetes within 20 years; this occurs more rapidly in the presence of IA-2A or ZnT8A, regardless of age, <i>HLA-DQ</i> genotype, and number of autoAbs.
The breakthrough discovery that the common polymorphism in zinc transporter <i>SLC30A8</i>/ZnT8 may increase susceptibility to type 2 diabetes provided novel insights into the role of zinc in diabetes.
Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.
The Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 is a Pseudogene in Guinea Pigs Potentially Contributing to Low Guinea Pig Islet Zinc Content.
Studies have demonstrated that susceptibility to type 2 diabetes (T2D) is influenced by common polymorphism in the zinc transporter 8 gene SLC30A8, providing novel insight into the role of zinc in diabetes.
Prevalence of diabetes and presence of autoantibodies against zinc transporter 8 and glutamic decarboxylase at diagnosis and at follow up of Graves' disease.
In this review, we summarize the structure, feature, functions, and polymorphisms of ZnT8 along with its association with diabetes and explore future study directions.
However, those with later onset type 1 diabetes had a modestly lower type 1 diabetes genetic risk score (0.268 vs 0.279; p < 0.001 [expected type 2 diabetes population median, 0.231]), a higher islet autoantibody prevalence (GAD-, islet antigen 2 [IA2]- or zinc transporter protein 8 [ZnT8]-positive) of 78% at 13 years vs 62% at 26 years of diabetes duration; (p = 0.02), and were less likely to identify as having type 1 diabetes (79% vs 100%; p < 0.001) vs those with young-onset disease.
Other outcomes are: (1) Any persistent confirmed beta-cell autoantibody (glutamic acid decarboxylase (GADA), IA-2A, autoantibodies to insulin (IAA) and zinc transporter 8 or tetraspanin 7), or diabetes, (2) Persistent confirmed IAA, (3) Persistent confirmed GADA and (4) Abnormal glucose tolerance or diabetes.