Growth hormone‐induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

Nellemann, Birgitte; Vendelbo, Mikkel Holm; Nielsen, Thomas S.; Bak, Ann Mosegaard; Høgild, Morten Lyng; Pedersen, Steen B.; Biensø, Rasmus S.; Pilegaard, Henriette; Møller, Niels; Jessen, Niels; Jørgensen, Jens O. L.

doi:10.1111/apha.12183

Cited by 37 publications

(38 citation statements)

References 46 publications

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“…PDH activity has been shown to be reduced in various tissues of animals and patients with diabetes or obesity-related conditions [16, 17]. PDH activity was also reduced in growth hormone-induced insulin resistance in human subjects [18]. It is possible that increased PDH phosphorylation in the liver of humans leads to decreased PDH activity and glucose intolerance.…”

Section: Discussionmentioning

confidence: 99%

Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia

Zhang

Ding

et al. 2017

Oncotarget

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AimGestational diabetes mellitus (GDM) has been shown to be associated with a high risk of diabetes in offspring. In mitochondria, the inhibition of pyruvate dehydrogenase (PDH) activity by PDH phosphorylation is involved in the development of diabetes. We aimed to determine the role of PDH phosphorylation in the liver in GDM-induced offspring glucose intolerance.ResultsPDH phosphorylation was increased in lymphocytes from the umbilical cord blood of the GDM patients and in high glucose-treated hepatic cells. Both the male and female offspring from GDM mice had elevated liver weights and glucose intolerance. Further, PDH phosphorylation was increased in the livers of both the male and female offspring from GDM mice, and elevated acetylation may have contributed to this increased phosphorylation.Materials and methodsWe obtained lymphocytes from umbilical cord blood collected from both normal and GDM pregnant women. In addition, we obtained the offspring of streptozotocin-induced GDM female pregnant mice. The glucose tolerance test was performed to assess glucose tolerance in the offspring. Further, Western blotting was conducted to detect changes in protein levels.ConclusionsIntrauterine hyperglycemia induced offspring glucose intolerance by inhibiting PDH activity, along with increased PDH phosphorylation in the liver, and this effect might be mediated by enhanced mitochondrial protein acetylation.

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Section: Discussionmentioning

confidence: 99%

Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia

Zhang

Ding

et al. 2017

Oncotarget

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“…However, several studies in human subjects have failed to document a similar effect [78,79,80]. There is, nevertheless, evidence to suggest that GH-induced insulin resistance in human skeletal muscle is causally linked to the concomitant increase in lipolysis [8] and that this is mediated via substrate competition between intermediates of glucose and fatty acids [81] (fig. 2).…”

Section: Discussionmentioning

confidence: 99%

Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care

Dal¹,

List²,

Jørgensen³

et al. 2015

Neuroendocrinology

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Patients with active acromegaly are frequently insulin resistant, glucose intolerant, and at risk for developing overt type 2 diabetes. At the same time, these patients have a relatively lean phenotype associated with mobilization and oxidation of free fatty acids. These features are reversed by curative surgical removal of the growth hormone (GH)-producing adenoma. Mouse models of acromegaly share many of these characteristics, including a lean phenotype and proneness to type 2 diabetes. There are, however, also species differences with respect to oxidation rates of glucose and fat as well as the specific mechanisms underlying GH-induced insulin resistance. The impact of acromegaly treatment on insulin sensitivity and glucose tolerance depends on the treatment modality (e.g. somatostatin analogs also suppress insulin secretion, whereas the GH antagonist restores insulin sensitivity). The interplay between animal research and clinical studies has proven useful in the field of acromegaly and should be continued in order to understand the metabolic actions of GH.

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“…GH activates lipolysis and reduces insulin sensitivity in mammalian AT [39]. In lactating dairy cattle, GH administration augments 2 to 6-fold AT response to adrenergic stimulation [40].…”

Section: Lipolysismentioning

confidence: 99%

Adipose tissue lipolysis and remodeling during the transition period of dairy cows

Contreras

Strieder‐Barboza

Raphael

2017

J Animal Sci Biotechnol

122

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Elevated concentrations of plasma fatty acids in transition dairy cows are significantly associated with increased disease susceptibility and poor lactation performance. The main source of plasma fatty acids throughout the transition period is lipolysis from adipose tissue depots. During this time, plasma fatty acids serve as a source of calories mitigating the negative energy balance prompted by copious milk synthesis and limited dry matter intake. Past research has demonstrated that lipolysis in the adipose organ is a complex process that includes not only the activation of lipolytic pathways in response to neural, hormonal, or paracrine stimuli, but also important changes in the structure and cellular distribution of the tissue in a process known as adipose tissue remodeling. This process involves an inflammatory response with immune cell migration, proliferation of the cellular components of the stromal vascular fraction, and changes in the extracellular matrix. This review summarizes current knowledge on lipolysis in dairy cattle, expands on the new field of adipose tissue remodeling, and discusses how these biological processes affect transition cow health and productivity.

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Growth hormone‐induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

Abstract: Competition between intermediates of glucose and fatty acids seems to play a causal role in insulin resistance induced by GH in human subjects.

Cited by 37 publications

References 46 publications

Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia

Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia

Glucose and Fat Metabolism in Acromegaly: From Mice Models to Patient Care

Adipose tissue lipolysis and remodeling during the transition period of dairy cows

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