Diabetes reduces β-cell mitochondria and induces distinct morphological abnormalities, which are reproducible by high glucose in vitro with attendant dysfunction

Ma, Zuheng; Wirström, Tina; Borg, Lisa; Larsson-Nyrén, Gerd; Hals, Ingrid; Bondo-Hansen, John; Grill, Valdemar; Björklund, Anneli

doi:10.4161/isl.20516

Cited by 22 publications

(17 citation statements)

References 26 publications

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“…In particular, electron microscopy revealed a loss of matrix density and disorganization of inner membrane cristae ( Figure 4(c) ). Interestingly, also animal models of diabetes showed a reduced number of mitochondria, with abnormal morphology, associated to mitochondrial dysfunction [ 53 ]. Notably, large lipid droplets that stock lipids as energy-rich storage compounds were observed.…”

Section: Discussionmentioning

confidence: 99%

Impact of Obesity and Hyperglycemia on Placental Mitochondria

Mandò

Anelli

Novielli

et al. 2018

Oxidative Medicine and Cellular Longevity

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A lipotoxic placental environment is recognized in maternal obesity, with increased inflammation and oxidative stress. These changes might alter mitochondrial function, with excessive production of reactive oxygen species, in a vicious cycle leading to placental dysfunction and impaired pregnancy outcomes. Here, we hypothesize that maternal pregestational body mass index (BMI) and glycemic levels can alter placental mitochondria. We measured mitochondrial DNA (mtDNA, real-time PCR) and morphology (electron microscopy) in placentas of forty-seven singleton pregnancies at elective cesarean section. Thirty-seven women were normoglycemic: twenty-one normal-weight women, NW, and sixteen obese women, OB/GDM(−). Ten obese women had gestational diabetes mellitus, OB/GDM(+). OB/GDM(−) presented higher mtDNA levels versus NW, suggesting increased mitochondrial biogenesis in the normoglycemic obese group. These mitochondria showed similar morphology to NW. On the contrary, in OB/GDM(+), mtDNA was not significantly increased versus NW. Nevertheless, mitochondria showed morphological abnormalities, indicating impaired functionality. The metabolic response of the placenta to impairment in obese pregnancies can possibly vary depending on several parameters, resulting in opposite strains acting when insulin resistance of GDM occurs in the obese environment, characterized by inflammation and oxidative stress. Therefore, mitochondrial alterations represent a feature of obese pregnancies with changes in placental energetics that possibly can affect pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

Impact of Obesity and Hyperglycemia on Placental Mitochondria

Mandò

Anelli

Novielli

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…These changes in morphology and function are associated with impaired GSIS through impaired oxidative phosphorylation, decreased mitochondrial Ca 2+ capacity and decline in ATP generation (28,29). In addition, disruption in Ca 2+ homeostasis (e.g.…”

Section: Factors Associated With Progressive Reduction Of Beta Cell Fmentioning

confidence: 99%

Diabetes and beta cell function: from mechanisms to evaluation and clinical implications

2013

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Diabetes is a complex, heterogeneous condition that has beta cell dysfunction at its core. Many factors (e.g. hyperglycemia/glucotoxicity, lipotoxicity, autoimmunity, inflammation, adipokines, islet amyloid, incretins and insulin resistance) influence the function of pancreatic beta cells. Chronic hyperglycaemia may result in detrimental effects on insulin synthesis/secretion, cell survival and insulin sensitivity through multiple mechanisms: gradual loss of insulin gene expression and other beta-cell specific genes; chronic endoplasmic reticulum stress and oxidative stress; changes in mitochondrial number, morphology and function; disruption in calcium homeostasis. In the presence of hyperglycaemia, prolonged exposure to increased free fatty acids result in accumulation of toxic metabolites in the cells (“lipotoxicity”), finally causing decreased insulin gene expression and impairment of insulin secretion. The rest of the factors/mechanisms which impact on the course of the disease are also discusses in detail.The correct assessment of beta cell function requires a concomitant quantification of insulin secretion and insulin sensitivity, because the two variables are closely interrelated. In order to better understand the fundamental pathogenetic mechanisms that contribute to disease development in a certain individual with diabetes, additional markers could be used, apart from those that evaluate beta cell function.The aim of the paper was to overview the relevant mechanisms/factors that influence beta cell function and to discuss the available methods of its assessment. In addition, clinical considerations are made regarding the therapeutical options that have potential protective effects on beta cell function/mass by targeting various underlying factors and mechanisms with a role in disease progression.

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“…Indeed, mitochondria in T2DM ␤-cells have been shown to exhibit both morphological and functional abnormalities that are not observed in control ␤-cells (81). Moreover, the release of proapoptotic proteins such as cytochrome c from damaged mitochondria is regarded as a key step in the initiation of ␤-cell apoptosis (76).…”

Section: The Ecs-mitochondrial Axis: a Regulator Of Pancreatic Islet mentioning

confidence: 99%

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

Lipina

Irving

Hundal

2014

American Journal of Physiology-Endocrinology and Metabolism

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Diabetes reduces β-cell mitochondria and induces distinct morphological abnormalities, which are reproducible by high glucose in vitro with attendant dysfunction

Cited by 22 publications

References 26 publications

Impact of Obesity and Hyperglycemia on Placental Mitochondria

Impact of Obesity and Hyperglycemia on Placental Mitochondria

Diabetes and beta cell function: from mechanisms to evaluation and clinical implications

Mitochondria: a possible nexus for the regulation of energy homeostasis by the endocannabinoid system?

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