Crystalline insulin

Scott, Darren M.; Fisher, A. M.

doi:10.1042/bj0291048

Cited by 91 publications

(30 citation statements)

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“…Since 1934 it has been known that zinc permits the formation of insulin crystals; two or more zinc atoms cause insulin to crystallise in hexamers [2]. We know that zinc-deficient animals have a lack of insulin in beta cells [3].…”

Section: Zinc and Diabetesmentioning

confidence: 99%

Zinc, zinc transporters and diabetes

Rungby

2010

Diabetologia

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The role of zinc in islet function has recently achieved new attention as a consequence of the identification of zinc transporter 8 (ZNT8) in islets, and the association of mutations in the gene for this zinc transporter with glucose intolerance and type 2 diabetes. ZNT8 is also an autoantigen associated with the appearance of type 1 diabetes. A number of experimental models have been employed to suggest how ZNT8 and other zinc transporters regulate beta cell insulin processing and possibly secretion. An additional role for the zinc transporters in regulating alpha cell function has been suggested. In this issue of Diabetologia, Wijesekara and colleagues, using a cell-specific Znt8 (also known as Slc30a8) knockout model, demonstrate that beta cell insulin processing and glucose tolerance is negatively affected after beta cell knock out of Znt8, whereas Znt8 knockout in alpha cells seems to have little effect on glucagon secretion or glucose tolerance. Although we are yet to see the therapeutic potential of these new findings, the area represents a field through which manipulation of islet function may eventually be possible.

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Section: Zinc and Diabetesmentioning

confidence: 99%

Zinc, zinc transporters and diabetes

Rungby

2010

Diabetologia

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“…The very nature of the substance(s) promoting crystallisation and the mechanisms of crystal formation remained unclear despite it being known that the pancreas contains high amounts of Zn. A few years later, Scott discovered that adding Zn to a phosphate-buffered solution containing insulin induced the formation of characteristic rhombohedral insulin crystals (3) . He then showed a direct effect of Zn ions on the action of insulin (4) .…”

Section: Insulin Diabetes and Zinc Researchmentioning

confidence: 99%

Zinc, pancreatic islet cell function and diabetes: new insights into an old story

Chimienti

2013

Nutr. Res. Rev.

105

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Zn is an essential trace element, involved in many different cellular processes. A relationship between Zn, pancreatic function and diabetes was suggested almost 70 years ago. To emphasise the importance of Zn in biology, the history of Zn research in the field of diabetes along with a general description of Zn transporter families will be reviewed. The paper will then focus on the effects of Zn on pancreatic b-cell function, including insulin synthesis and secretion, Zn signalling in the pancreatic islet, the redox functions of Zn and its target genes. The recent association of two 'Zn genes', i.e. metallothionein (MT) and Zn transporter 8 (SLC 30A8 ), with type 2 diabetes at the genetic level and with insulin secretion in clinical studies offers a potential new way to identify new drug targets to modulate Zn homeostasis directly in b-cells. The action of Zn for insulin action in its target organs, as Zn signalling in other pancreatic islet cells, will be addressed. Therapeutic Zn-insulin preparations and the influence of Zn and Zn transporters in type 1 diabetes will also be discussed. An extensive review of the literature on the clinical studies using Zn supplementation in the prevention and treatment of both types of diabetes, including complications of the disease, will evaluate the overall beneficial effects of Zn supplementation on blood glucose control, suggesting that Zn might be a candidate ion for diabetes prevention and therapy. Clearly, the story of the links between Zn, pancreatic islet cells and diabetes is only now unfolding, and we are presently only at the first chapter.

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“…It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].…”

mentioning

confidence: 99%

“…The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].…”

mentioning

confidence: 99%

Zinc and diabetes

Chabosseau

Rutter

2016

Archives of Biochemistry and Biophysics

150

104

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Zn 2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn 2+ 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. Abbreviation ISG: Insulin Secreting Granules; T2D: Type 2 Diabetes; T1D: Type 1 Diabetes; 2 Diabetes mellitus is a common metabolic disease, affecting approximately 9% of the adult population worldwide. It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].These early studies, as well as much more recent findings showing association between T2D risk and the inheritance of gene variants encoding a critical β cell Zn 2+ transporter, ZnT8[5] have generated considerable interest in the role of Zn 2+ in diabetes aetiology and as a possible therapeutic target [6]. Zinc and the diabetic patientScott and Fisher were the first to report a direct link between zinc and diabetes in patients.While assessing the insulin content in the pancreas of diabetic patients compared to nondiabetic cadavers, they showed that in the former group zinc content was reduced by 75 % [7].Epidemiological studies also demonstrated that diabetes and whole body zinc status are associated [8][9][10][11]. In T1D and T2D patients, serum zinc levels are significantly decreased [9][10][11], this being associated with an increased zinc urinary loss [8].Zinc may have important anti-oxidant properties, as it acts as a cofactor of the superoxide dismutase enzyme which regulates the detoxification of reactive oxygen species, regulating the expression and protecting against the oxidative stress induced by chronic hyperglycaemia (for review, [12]). Furthermore, zinc inhibits alpha-ketoglutarate-dependent mitochondrial respiration suggesting that Zn 2+ can interfere with mitochondrial antioxidant production and may also stimulate production of reactive oxygen [13].Zinc supplementation h...

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Crystalline insulin

Cited by 91 publications

References 1 publication

Zinc, zinc transporters and diabetes

Zinc, zinc transporters and diabetes

Zinc, pancreatic islet cell function and diabetes: new insights into an old story

Zinc and diabetes

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