Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

Keller, Ulrich; Lustenberger, M.; Müller-Brand, Jan; Gerber, P. P. G.; Stauffacher, Werner

doi:10.1002/dmr.5610050306

Cited by 35 publications

(18 citation statements)

References 52 publications

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“…The somewhat lower rate of NEFA uptake in the pregnant group did not appear to limit gluconeogenesis, since the gluconeogenic flux rate was nearly identical to the gluconeogenic contribution to NHGO in both groups. Ketogenesis was not lower in pregnant vs. nonpregnant dogs in response to insulin-induced hypoglycemia, even though factors that strongly influence ketogenesis, such as glucagon (30), norepinephrine (32), and NEFA availability, were reduced in the pregnant dogs. Although insulin normally suppresses ketogenesis, even when the fatty acid supply is maintained (31), it appears that the increase in either epinephrine or sympathetic nervous activity might have interfered with that action and maintained ketone production in both groups.…”

Section: Discussionmentioning

confidence: 86%

Pregnancy impairs the counterregulatory response to insulin-induced hypoglycemia in the dog

Connolly

Aglione

Smith

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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The impact of pregnancy on the counterregulatory response to insulin-induced hypoglycemia was examined in six nonpregnant (NP) and six pregnant (P; 3rd trimester) conscious dogs by tracer and arteriovenous difference techniques. After basal sampling, insulin was infused intraportally at 30 pmol.kg(-1).min(-1) for 180 min. Insulin rose from 70 +/- 15 to 1,586 +/- 221 pmol/l and 27 +/- 4 to 1,247 +/- 61 pmol/l in the 3rd h in NP and P, respectively. Arterial glucose fell from 5.9 +/- 0.2 to 2.3 +/- 0.2 mmol/l in P. Glucose was infused in NP to equate the rate of fall of glucose and the steady-state concentrations in the groups (5.9 +/- 0.2 to 2.3 +/- 0.1 mmol/l in NP). Glucagon was 32 +/- 6, 69 +/- 11, and 48 +/- 10 ng/l (basal and 1st and 3rd h) in NP, but the response was attenuated in P (34 +/- 5, 46 +/- 6, 41 +/- 9 ng/l). Cortisol and epinephrine rose similarly in both groups, but norepinephrine rose more in NP (Delta3.01 +/- 0.46 and Delta1.31 +/- 0.13 nmol/l, P < 0.05). Net hepatic glucose output (NHGO; micromol.kg(-1).min(-1)) increased from 10.6 +/- 1.8 to 21.2 +/- 3.3 in NP (3rd h) but did not increase in P (15.1 +/- 1.5 to 15.3 +/- 2.8 micromol.kg(-1).min(-1), P < 0.05 between groups). The glycogenolytic contribution to NHGO in NP increased from 5.8 +/- 0.7 to 10.4 +/- 2.5 micromol.kg(-1).min(-1) by 90 min but steadily declined in P. The increase in glycerol levels and the gluconeogenic contribution to NHGO were 50% less in P than in NP, but ketogenesis did not differ. The glucagon and norepinephrine responses to insulin-induced hypoglycemia are blunted in late pregnancy in the dog, impacting on the magnitude of the metabolic responses to the fall in glucose.

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Section: Discussionmentioning

confidence: 86%

Pregnancy impairs the counterregulatory response to insulin-induced hypoglycemia in the dog

Connolly

Aglione

Smith

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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“…Increased influx of fatty acids to the liver induces their β-oxidation and subsequent ketogenesis. Among catabolic hormones, epinephrine and norepinephrine, which drive “fight or flight” reactions to stress, are particularly strong activators of lipolysis, fatty acid oxidation and ketogenesis, and remain active regardless of insulin levels [8,9]. …”

Section: Regulation Of Ketogenesis—the Role Of Pparαmentioning

confidence: 99%

Regulation of Ketone Body Metabolism and the Role of PPARα

Grabacka

Pierzchalska

Dean

et al. 2016

IJMS

247

202

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Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.

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“…Ketone clearance is linear with ketone concentration, so as ketone levels fall, clearance also falls. There is also evidence that hyperthyroidism increases clearance of ketones (16). We speculate that with the initiation of thyroxine-lowering treatment, ketone clearance decreased more rapidly than production, allowing ketones to transiently accumulate in the plasma.…”

Section: Discussionmentioning

confidence: 91%

Nondiabetic Ketoacidosis Caused by Severe Hyperthyroidism

Wood

Kinlaw

2004

Thyroid

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Severe hyperthyroidism is not included in the traditional differential diagnosis of ketoacidosis. However, thyroid hormone has well-documented lipolytic effects on adipocytes and may also promote hepatic beta-oxidation. We present a case in which a woman with severe hyperthyroidism developed otherwise unexplained ketoacidosis during the acute phase of her illness. We propose that thyrotoxicosis was a significant contributor to ketoacidosis in this patient and that severe hyperthyroidism should be added to the differential diagnosis of ketoacidosis.

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Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

Cited by 35 publications

References 52 publications

Pregnancy impairs the counterregulatory response to insulin-induced hypoglycemia in the dog

Pregnancy impairs the counterregulatory response to insulin-induced hypoglycemia in the dog

Regulation of Ketone Body Metabolism and the Role of PPARα

Nondiabetic Ketoacidosis Caused by Severe Hyperthyroidism

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