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Find video protocols related to scientific articles indexed in Pubmed.
Adipsin is an adipokine that improves ? cell function in diabetes.
Cell
PUBLISHED: 03-19-2014
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A hallmark of type 2 diabetes mellitus (T2DM) is the development of pancreatic ? cell failure, which results in insulinopenia and hyperglycemia. We show that the adipokine adipsin has a beneficial role in maintaining ? cell function. Animals genetically lacking adipsin have glucose intolerance due to insulinopenia; isolated islets from these mice have reduced glucose-stimulated insulin secretion. Replenishment of adipsin to diabetic mice treated hyperglycemia by boosting insulin secretion. We identify C3a, a peptide generated by adipsin, as a potent insulin secretagogue and show that the C3a receptor is required for these beneficial effects of adipsin. C3a acts on islets by augmenting ATP levels, respiration, and cytosolic free Ca(2+). Finally, we demonstrate that T2DM patients with ? cell failure are deficient in adipsin. These findings indicate that the adipsin/C3a pathway connects adipocyte function to ? cell physiology, and manipulation of this molecular switch may serve as a therapy in T2DM.
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A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators.
Nat. Struct. Mol. Biol.
PUBLISHED: 08-11-2013
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Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin release and hepatic metabolism, and its loss of function is implicated in diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in diabetes; however, clinical data indicate that their benefits can be offset by hypoglycemia, owing to marked allosteric enhancement of the enzymes glucose affinity. We show that a phosphomimetic of the BCL-2 homology 3 (BH3) ?-helix derived from human BAD, a GK-binding partner, increases the enzyme catalytic rate without dramatically changing glucose affinity, thus providing a new mechanism for pharmacologic activation of GK. Remarkably, BAD BH3 phosphomimetic mediates these effects by engaging a new region near the enzymes active site. This interaction increases insulin secretion in human islets and restores the function of naturally occurring human GK mutants at the active site. Thus, BAD phosphomimetics may serve as a new class of GKAs.
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The GTPase Rab37 Participates in the Control of Insulin Exocytosis.
PLoS ONE
PUBLISHED: 01-01-2013
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Rab37 belongs to a subclass of Rab GTPases regulating exocytosis, including also Rab3a and Rab27a. Proteomic studies indicate that Rab37 is associated with insulin-containing large dense core granules of pancreatic ?-cells. In agreement with these observations, we detected Rab37 in extracts of ?-cell lines and human pancreatic islets and confirmed by confocal microscopy the localization of the GTPase on insulin-containing secretory granules. We found that, as is the case for Rab3a and Rab27a, reduction of Rab37 levels by RNA interference leads to impairment in glucose-induced insulin secretion and to a decrease in the number of granules in close apposition to the plasma membrane. Pull-down experiments revealed that, despite similar functional effects, Rab37 does not interact with known Rab3a or Rab27a effectors and is likely to operate through a different mechanism. Exposure of insulin-secreting cells to proinflammatory cytokines, fatty acids or oxidized low-density lipoproteins, mimicking physiopathological conditions that favor the development of diabetes, resulted in a decrease in Rab37 expression. Our data identify Rab37 as an additional component of the machinery governing exocytosis of ?-cells and suggest that impaired expression of this GTPase may contribute to defective insulin release in pre-diabetic and diabetic conditions.
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The GTPase RalA regulates different steps of the secretory process in pancreatic beta-cells.
PLoS ONE
PUBLISHED: 01-16-2009
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RalA and RalB are multifuntional GTPases involved in a variety of cellular processes including proliferation, oncogenic transformation and membrane trafficking. Here we investigated the mechanisms leading to activation of Ral proteins in pancreatic beta-cells and analyzed the impact on different steps of the insulin-secretory process.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.