Accelerated decline in hepatic glucose production during fasting in normal women compared with men

Clore, John N.; Glickman, Penny S.; Helm, S T; Nestler, John E.; Blackard, William G.

doi:10.1016/0026-0495(89)90047-4

Cited by 26 publications

(16 citation statements)

References 19 publications

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“…To our knowledge, there is no general consensus regarding sex differences in plasma glycerol levels in humans. However, several groups have reported higher plasma glycerol levels in women than in men in response to both fasting and moderate-intensity exercise (5,6,14,25). This sex-specific difference has also been observed in exercising type 1 diabetics (10).…”

Section: Discussionmentioning

confidence: 89%

“…Furthermore several observations have been made of females responding to both fasting and moderate-intensity exercise with higher plasma glycerol levels than males (5,6,14,25).…”

mentioning

confidence: 97%

“…production to a greater extent than males during starvation (5) and respond to starvation with lower blood glucose levels (24). Furthermore several observations have been made of females responding to both fasting and moderate-intensity exercise with higher plasma glycerol levels than males (5,6,14,25).…”

mentioning

confidence: 98%

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Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

Lebeck

Gena

O’Neill

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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In starvation, glycerol is released from adipose tissue and serves as an important precursor for hepatic gluconeogenesis. By unknown sex-specific mechanisms, women suppress the endogenous glucose production better than men and respond to metabolic stress with higher plasma glycerol levels. Hepatic glycerol uptake is facilitated by aquaporin-9 (AQP9), a broad-selectivity neutral solute channel, and represents an insulin-regulated step in supplying gluconeogenesis with glycerol. In the present study, hepatic AQP9 abundance was increased 2.6-fold in starved male rats as assessed by immunoblotting and immunohistochemistry. By contrast, starvation had no significant effect on hepatic AQP9 expression in female rats. Coordinately, plasma glycerol levels remained unchanged with starvation in male rats, whereas it was increased in female rats. The different responses to starvation were paralleled by higher glycerol permeability in basolateral hepatocyte membranes from starved male rats compared with starved females. Ovariectomy led to a starvation-response pattern identical to that observed in male rats with increased hepatic AQP9 expression and unchanged plasma glycerol levels. In cultured hepatocytes, 17β-estradiol and the selective estrogen receptor α-agonist, propyl pyrazole triol, caused a decrease in AQP9 expression. Our results support that a sex-specific regulation of the hepatic glycerol channel AQP9 during starvation contributes to the higher plasma glycerol levels observed in women during fasting and possibly results in a lower cytosolic availability of glycerol. Furthermore, the sexual dimorphism in the hepatic handling of glycerol during starvation might be explained by 17β-estradiol preventing the starvation-induced increase in hepatic AQP9 abundance.

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Section: Discussionmentioning

confidence: 89%

“…Furthermore several observations have been made of females responding to both fasting and moderate-intensity exercise with higher plasma glycerol levels than males (5,6,14,25).…”

mentioning

confidence: 97%

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Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

Lebeck

Gena

O’Neill

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Plasma glucose levels decrease during fasting, which is a normal physiological finding (20,60,73). These decreasing glucose levels have been suggested to result from the slowly decreasing EGP (20, 60) that correlates very well with the plasma glucose level in the postabsorptive state (31).…”

Section: Glucose Turnover During Starvationmentioning

confidence: 94%

Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation

Soeters

Schooneman

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

143

107

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The human organism has tools to cope with metabolic challenges like starvation that are crucial for survival. Lipolysis, lipid oxidation, ketone body synthesis, tailored endogenous glucose production and uptake, and decreased glucose oxidation serve to protect against excessive erosion of protein mass, which is the predominant supplier of carbon chains for synthesis of newly formed glucose. The starvation response shows that the adaptation to energy deficit is very effective and coordinated with different adaptations in different organs. From an evolutionary perspective, this lipid-induced effect on glucose oxidation and uptake is very strong and may therefore help to understand why insulin resistance in obesity and type 2 diabetes mellitus is difficult to treat. The importance of reciprocity in lipid and glucose metabolism during human starvation should be taken into account when studying lipid and glucose metabolism in general and in pathophysiological conditions in particular.

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“…Whether a similar gender-specific response to exercise also applies to visceral adipose tissue (VAT) remains to be investigated. However, the higher need for AQP7 to support glycerol efflux from adipose tissue in women seems well related to the higher plasma glycerol level found in women in response to metabolic stress such as fasting (Hales et al 1965, Clore et al 1989, Mittendorfer et al 2001) and exercise (Davis et al 2000, Galassetti et al 2002, Mittendorfer et al 2002.…”

Section: Figurementioning

confidence: 99%

Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver

Lebeck

2014

Journal of Molecular Endocrinology

103

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Obesity and secondary development of type 2 diabetes (T2D) are major health care problems throughout the developed world. Accumulating evidence suggest that glycerol metabolism contributes to the pathophysiology of obesity and T2D. Glycerol is a small molecule that serves as an important intermediate between carbohydrate and lipid metabolism. It is stored primarily in adipose tissue as the backbone of triglyceride (TG) and during states of metabolic stress, such as fasting and diabetes, it is released for metabolism in other tissues. In the liver, glycerol serves as a gluconeogenic precursor and it is used for the esterification of free fatty acid into TGs. Aquaporin 7 (AQP7) in adipose tissue and AQP9 in the liver are transmembrane proteins that belong to the subset of AQPs called aquaglyceroporins. AQP7 facilitates the efflux of glycerol from adipose tissue and AQP7 deficiency has been linked to TG accumulation in adipose tissue and adult onset obesity. On the other hand, AQP9 expressed in liver facilitates the hepatic uptake of glycerol and thereby the availability of glycerol for de novo synthesis of glucose and TG that both are involved in the pathophysiology of diabetes. The aim of this review was to summarize the current knowledge on the role of the two glycerol channels in controlling glycerol metabolism in adipose tissue and liver. Glycerol metabolismThe metabolic switching between feeding and fasting is central to everyday life and involves tight hormonal control with effects on muscle, adipose tissue, and liver that maintains an adequate handling of metabolic precursors to support energy demands. One of the molecules affected by metabolic switching is glycerol, which is a small 3-carbon alcohol that in the fed state is stored as the backbone of triglyceride (TG) mainly in adipose tissue.In the fed state, after ingestion of dietary fats (w90% TG), !30% of TG is fully hydrolyzed into free fatty acids (FFA) and glycerol. Glycerol rapidly enters the enterocytes of the small intestine and thereafter the circulation through the portal vein and is primarily metabolized by the liver (Lin 1977). In adipose tissue, the activity of glycerol kinase (GlyK), that catalyzes the initial phosphorylation of glycerol into glycerol-3-phosphate (G3P), is negligible and therefore glycerol is not normally utilized in adipose tissue. Instead G3P used for the synthesis of TG in the fed state is derived from glycolysis.During states of increased energy demand, such as fasting and exercise, adipocyte lipolysis is increased by activation of adipose TG lipase and hormone-sensitive

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Accelerated decline in hepatic glucose production during fasting in normal women compared with men

Cited by 26 publications

References 19 publications

Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

Estrogen prevents increased hepatic aquaporin-9 expression and glycerol uptake during starvation

Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation

Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver

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