The PI3K/AKT pathway in obesity and type 2 diabetes

Huang, Xuming; Liu, Guihua; Guo, Jiao; Su, Zhixing

doi:10.7150/ijbs.27173

Cited by 1,057 publications

(848 citation statements)

References 172 publications

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“…This suggested the deficits lay within peripheral tissues, skeletal muscle or adipose tissue, with PI3K/AKT signalling known to play an essential role in insulin‐mediated glucose uptake in these peripheral tissues (Huang et al . ). Supporting this, we did find moderate alterations in AKT levels in adipose tissue, both total AKT and activated AKT, measured by phosphorylation at Thr 308 .…”

Section: Discussionmentioning

confidence: 97%

Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure

Nguyen

Steane

Moritz

et al. 2019

The Journal of Physiology

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Key points Prenatal alcohol exposure has the potential to affect fetal development and programme chronic disease in offspring. Previous preclinical models typically use high, chronic doses of alcohol throughout pregnancy to examine effects on offspring, particularly on the brain and behaviour. In this study we use a rat model of moderate, acute, prenatal alcohol exposure to determine if this can be detrimental to maintenance of glucose homeostasis in adolescent and adult offspring. Although female offspring were relatively unaffected, there was evidence of insulin resistance in 6‐month‐old male offspring exposed to prenatal alcohol, suggestive of a pre‐diabetic state. This result suggests that even a relatively low‐dose, acute exposure to alcohol during pregnancy can still programme metabolic dysfunction in a sex‐specific manner. Abstract Alcohol consumption is highly prevalent amongst women of reproductive age. Given that approximately 50% of pregnancies are unplanned, alcohol has the potential to affect fetal development and programme chronic disease in offspring. We examined the effect of an acute but moderate prenatal alcohol exposure (PAE) on glucose metabolism, lipid levels and dietary preference in adolescent and/or adult rat offspring. Pregnant Sprague–Dawley rats received an oral gavage of ethanol (1 g kg−1 maternal body weight, n = 9 dams) or an equivalent volume of saline (control, n = 8 dams) at embryonic days 13.5 and 14.5. PAE resulted in a blood alcohol concentration of 0.05–0.06% 1 h post‐gavage in dams. Fasting blood glucose concentration was not affected by PAE in offspring at any age, nor were blood glucose levels during a glucose tolerance test (GTT) in 6‐month‐old offspring (P > 0.5). However, there was evidence of insulin resistance in PAE male offspring at 6 months of age, with significantly elevated fasting plasma insulin (P = 0.001), a tendency for increased first phase insulin secretion during the GTT and impaired glucose clearance following an insulin challenge (P = 0.007). This was accompanied by modest alterations in protein kinase B (AKT) signalling in adipose tissue. PAE also resulted in reduced calorie consumption by offspring compared to controls (P = 0.04). These data suggest that a relatively low‐level, acute PAE programmes metabolic dysfunction in offspring in a sex‐specific manner. These results highlight that alcohol consumption during pregnancy has the potential to affect the long‐term health of offspring.

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Section: Discussionmentioning

confidence: 97%

Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure

Nguyen

Steane

Moritz

et al. 2019

The Journal of Physiology

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“…We indeed identified deleterious changes to the insulin signaling pathway, including the Akt protein signaling kinase (Akt) and PI3K. Damage to this pathway in various tissues has been linked to insulin resistance (Huang, Liu, Guo, & Su, 2018). The three Akt isoforms have differential physiological functions but loss of function in one isoform is compensated by another.…”

Section: Discussionmentioning

confidence: 99%

Adaptations of energy metabolism in cetaceans have consequences for their response to foraging disruption

Derous

Sahu

Douglas

et al. 2019

Preprint

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Cetaceans have varied their anatomical structure, physiology and metabolism to adapt to the challenges of aquatic life. Key to this change is the deposition of blubber. This adipose tissue plays a significant regulatory and signaling role in mammalian metabolism. As foraging disruption by human activities is emerging as a key conservation threat for cetaceans, we need to understand how selection for aquatic life might have altered key nutrient sensing pathways associated with adipose signaling. We compared selection pressure on those energy metabolism biological pathways by contrasting the rate of substitution observed in genes associated with them in cetacean and artiodactyl genomes. We then estimated the likely consequence of these selection pressures for pathway functions. Here we show that genes involved in the insulin, mTOR, SIRT and NF-κB pathways were under significant positive selection in cetaceans compared to their terrestrial sister taxon. Our results suggest these genes may have been positively selected to adapt to a glucose-poor diet and it is unlikely that fat depots signaling function in the same manner as in terrestrial mammals. Secondary adaptation to life in water significantly affected functions in nutrient sensing pathways in cetaceans. Insulin is not likely to play the same role in energy balance as it does in terrestrial mammals and adiposity is not likely to have the deleterious health consequences it has in terrestrial mammals. The physiological ecology of cetacean fat deposition, and therefore its value as a condition index, needs to be interpreted in this evolutionary context.

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“…The phosphoinositide 3-kinase (PI3K) signaling pathway, a signal transduction system downstream of an insulin receptor (IR), is a key factor in the translocation of the glucose transporter protein from intracellular compartments to plasma membrane (10). IRs are present in most mammalian cells, and insulin-IR binding results in the activation of several phosphorylation-dephosphorylation cascades (11).…”

mentioning

confidence: 99%

White sweet potato ameliorates hyperglycemia and regenerates pancreatic islets in diabetic mice

Shih

Chen

Varga

et al. 2020

Food & Nutrition Research

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The PI3K/AKT pathway in obesity and type 2 diabetes

Cited by 1,057 publications

References 172 publications

Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure

Prenatal alcohol exposure programmes offspring disease: insulin resistance in adult males in a rat model of acute exposure

Adaptations of energy metabolism in cetaceans have consequences for their response to foraging disruption

White sweet potato ameliorates hyperglycemia and regenerates pancreatic islets in diabetic mice

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