Novel genes underlying beta cell survival in metabolic stress

Singh, Himadri; Farouk, Mohammed; Bose, Barish Baran; Singh, Prabhakar

doi:10.6026/97320630009037

Cited by 14 publications

(9 citation statements)

References 49 publications

(47 reference statements)

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“…The mammalian sda ortholog, alanyl aminopeptidase ( ANPEP ), is a receptor metalloproteinase. ANPEP has been associated with regulating networks involved in the development of type 2 diabetes [ 174 ] and may underlie pancreatic β cell fate during metabolic stress [ 175 ]. RNAi of Limpet ( Lmpt ) affects females food intake.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Genetics of Food Intake in Drosophila melanogaster

et al. 2015

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Food intake is an essential animal activity, regulated by neural circuits that motivate food localization, evaluate nutritional content and acceptance or rejection responses through the gustatory system, and regulate neuroendocrine feedback loops that maintain energy homeostasis. Excess food consumption in people is associated with obesity and metabolic and cardiovascular disorders. However, little is known about the genetic basis of natural variation in food consumption. To gain insights in evolutionarily conserved genetic principles that regulate food intake, we took advantage of a model system, Drosophila melanogaster, in which food intake, environmental conditions and genetic background can be controlled precisely. We quantified variation in food intake among 182 inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel (DGRP). We found significant genetic variation in the mean and within-line environmental variance of food consumption and observed sexual dimorphism and genetic variation in sexual dimorphism for both food intake traits (mean and variance). We performed genome wide association (GWA) analyses for mean food intake and environmental variance of food intake (using the coefficient of environmental variation, CV E, as the metric for environmental variance) and identified molecular polymorphisms associated with both traits. Validation experiments using RNAi-knockdown confirmed 24 of 31 (77%) candidate genes affecting food intake and/or variance of food intake, and a test cross between selected DGRP lines confirmed a SNP affecting mean food intake identified in the GWA analysis. The majority of the validated candidate genes were novel with respect to feeding behavior, and many had mammalian orthologs implicated in metabolic diseases.

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Section: Discussionmentioning

confidence: 99%

Quantitative Genetics of Food Intake in Drosophila melanogaster

et al. 2015

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“…4). Perhaps expansion of PMPs in these islets is associated with b-cell stress due to aging (58,59).…”

Section: Discussionmentioning

confidence: 99%

Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production

et al. 2014

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Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for b-cell loss since their b-cell-producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that b-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward b-cells in mouse and human. These effects are dynamic and correlate with functional b-cell regeneration when conditions allow.

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“…Other symptoms of KCS2 include severe proportionate short stature, radiological bone anomalies, eye abnormalities and hypocalcemia owing to hypoparathyroidism (reviewed in [82]). FAM111A has been reported to be a host-range restriction factor [86] and shown to be an important component of the cell’s replication machinery near DNA forks, consistent with its proposed role in cancer and cell survival [87–89]. However, it is unclear how this function would link to hypomagnesemia.…”

Section: Hereditary Hypomagnesemiasmentioning

confidence: 97%

Genetic causes of hypomagnesemia, a clinical overview

et al. 2016

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Magnesium is essential to the proper functioning of numerous cellular processes. Magnesium ion (Mg2+) deficits, as reflected in hypomagnesemia, can cause neuromuscular irritability, seizures and cardiac arrhythmias. With normal Mg2+ intake, homeostasis is maintained primarily through the regulated reabsorption of Mg2+ by the thick ascending limb of Henle’s loop and distal convoluted tubule of the kidney. Inadequate reabsorption results in renal Mg2+ wasting, as evidenced by an inappropriately high fractional Mg2+ excretion. Familial renal Mg2+ wasting is suggestive of a genetic cause, and subsequent studies in these hypomagnesemic families have revealed over a dozen genes directly or indirectly involved in Mg2+ transport. Those can be classified into four groups: hypercalciuric hypomagnesemias (encompassing mutations in CLDN16, CLDN19, CASR, CLCNKB), Gitelman-like hypomagnesemias (CLCNKB, SLC12A3, BSND, KCNJ10, FYXD2, HNF1B, PCBD1), mitochondrial hypomagnesemias (SARS2, MT-TI, Kearns–Sayre syndrome) and other hypomagnesemias (TRPM6, CNMM2, EGF, EGFR, KCNA1, FAM111A). Although identification of these genes has not yet changed treatment, which remains Mg2+ supplementation, it has contributed enormously to our understanding of Mg2+ transport and renal function. In this review, we discuss general mechanisms and symptoms of genetic causes of hypomagnesemia as well as the specific molecular mechanisms and clinical phenotypes associated with each syndrome.

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Novel genes underlying beta cell survival in metabolic stress

Cited by 14 publications

References 49 publications

Quantitative Genetics of Food Intake in Drosophila melanogaster

Quantitative Genetics of Food Intake in Drosophila melanogaster

Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production

Genetic causes of hypomagnesemia, a clinical overview

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