Proinflammatory cytokines mediate pancreatic β-cell specific alterations to Golgi morphology via iNOS-dependent mitochondrial inhibition.

Type 1 diabetes (T1D) is caused by the selective autoimmune ablation of pancreatic β-cells. Emerging evidence reveals β-cell secretory dysfunction arises early in T1D development and may contribute to diseases etiology; however, the underlying mechanisms are not well understood. Our data reveal that proinflammatory cytokines elicit a complex change in the β-cell's Golgi structure and function.

Loss of the Golgi-localized v-ATPase subunit does not alter insulin granule formation or pancreatic islet β-cell function.

Delayed Golgi export of proinsulin has recently been identified as an underlying mechanism leading to insulin granule loss and β-cell secretory defects in type 2 diabetes (T2D). Because acidification of the Golgi lumen is critical for proinsulin sorting and delivery into the budding secretory granule, we reasoned that dysregulation of Golgi pH may contribute to proinsulin trafficking defects. In this report, we examined pH regulation of the Golgi and identified a partial alkalinization of the Golgi lumen in a diabetes model.

ER Redox Homeostasis Regulates Proinsulin Trafficking and Insulin Granule Formation in the Pancreatic Islet β-Cell.

Defects in the pancreatic β-cell's secretion system are well-described in type 2 diabetes (T2D) and include impaired proinsulin processing and a deficit in mature insulin-containing secretory granules; however, the cellular mechanisms underlying these defects remain poorly understood. To address this, we used an in situ fluorescent pulse-chase strategy to study proinsulin trafficking. We show that insulin granule formation and the appearance of nascent granules at the plasma membrane are decreased in rodent and cell culture models of prediabetes and hyperglycemia.

Nutrient Regulation of Pancreatic Islet β-Cell Secretory Capacity and Insulin Production.

Pancreatic islet β-cells exhibit tremendous plasticity for secretory adaptations that coordinate insulin production and release with nutritional demands. This essential feature of the β-cell can allow for compensatory changes that increase secretory output to overcome insulin resistance early in Type 2 diabetes (T2D). Nutrient-stimulated increases in proinsulin biosynthesis may initiate this β-cell adaptive compensation; however, the molecular regulators of secretory expansion that accommodate the increased biosynthetic burden of packaging and producing additional insulin granules, such as enhanced ER and Golgi functions, remain poorly defined.

The Test of Masticating and Swallowing Solids (TOMASS): Normative data for two crackers available in the Scandinavian and international markets.

Purpose: To establish normative data of crackers common in the Scandinavian and international markets for use in the Test of Masticating and Swallowing Solids (TOMASS), and to investigate possible sex and age effects on masticatory performances.

Method: 234 healthy participants (>20 years of age) were asked to either ingest the Göteborgskex Guld Marie™ cracker ( = 234) or to ingest both a Guld Marie cracker and a Tuc Original™ cracker ( = 115). Quantifiable measures of masticatory performance (number of bites, number of chewing cycles, number of swallows, and total time) were observed during TOMASS for each participant, directly on-site or by video recording.