Glucose Metabolism and Regulation: Beyond Insulin and Glucagon

Aronoff, Stephen L.; Berkowitz, Kathy J.; Shreiner, Barb; Want, Laura L.

doi:10.2337/diaspect.17.3.183

Cited by 472 publications

(418 citation statements)

References 72 publications

(49 reference statements)

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“…Plasma glucose is derived from the feed, glycogen, and by gluconeogenesis, and it is regulated by several hormones, mainly glucagon and insulin. Glucagon increases plasma glucose concentration through stimulation of gluconeogenesis and glycogenolysis (Aronoff et al, 2004;Taborsky, 2010). Changes in glucagon secretion from the physiological range results in changes of plasma glucose concentration (Taborsky, 2010); some substrates, such as NEFA and ketone bodies, suppress glucagon secretion (Gerich et al, 1974;1976;Goberna et al, 1974).…”

Section: Discussionmentioning

confidence: 99%

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism

Zarrin

Matteis

Vernay

et al. 2013

Journal of Dairy Science

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Elevation of ketone bodies in dairy cows frequently occurs in early lactation, usually concomitantly with a lack of energy and glucose. The objective of this study was to induce an elevated plasma β-hydroxybutyrate (BHBA) concentration over 48 h in mid-lactating dairy cows (i.e., during a period of positive energy balance and normal glucose plasma concentrations). Effects of BHBA infusion on feed intake, metabolism, and performance were investigated. Thirteen cows were randomly assigned to 1 of 2 infusion groups, including an intravenous infusion with Na-dl-β-OH-butyrate (1.7 mol/L) to achieve a plasma concentration of 1.5 to 2.0 mmol/L of BHBA (HyperB; n = 5), or an infusion of 0.9% saline solution (control; n = 8). Blood was sampled before and hourly during the 48 h of infusion. In the liver, mRNA transcripts related to gluconeogenesis (pyruvate carboxylase, glucose 6-phosphatase, mitochondrial phosphoenolpyruvate carboxykinase), phosphofructokinase, pyruvate dehydrogenase complex, and fatty acid synthesis (acetyl-coenzyme A carboxylase, fatty acid synthase) were measured by real-time PCR. Glyceraldehyde-3-phosphate dehydrogenase and ubiquitin were used as housekeeping genes. Changes (difference between before and after 48-h infusion) during the infusion period were evaluated by ANOVA with treatment as fixed effect, and area under the curve of variables was calculated on the second day of experiment. The plasma BHBA concentration in HyperB cows was 1.74 ± 0.02 mmol/L (mean ± SE) compared with 0.59 ± 0.02 mmol/L for control cows. The change in feed intake, milk yield, and energy corrected milk did not differ between the 2 experimental groups. Infusion of BHBA reduced the plasma glucose concentration (3.47 ± 0.11 mmol/L) in HyperB compared with control cows (4.11 ± 0.08 mmol/L). Plasma glucagon concentration in HyperB was lower than the control group. All other variables measured in plasma were not affected by treatment. In the liver, changes in mRNA abundance for the selected genes were similar between 2 groups. Results demonstrate that intravenous infusion of BHBA decreased plasma glucose concentration in dairy cows, but this decrease could not be explained by alterations in insulin concentrations or key enzymes related to gluconeogenesis. Declined glucose concentration is likely functionally related to decreased plasma glucagon concentration.

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Section: Discussionmentioning

confidence: 99%

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism

Zarrin

Matteis

Vernay

et al. 2013

Journal of Dairy Science

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Section: 2mentioning

confidence: 99%

“…3 These hormones act on several target tissues, including muscle, liver, adipocyte, and brain to regulate glucose levels. 3 Insulin is a key glucoregulatory hormone, produced by pancreatic β-cells, whose levels are low during the fasting state, whereas they increase during the postprandial phase, when insulin stimulates utilization of dietary glucose by peripheral tissues, and in the meantime represses hepatic glucose production. 4 Another important hormone regulating glucose metabolism is glucagon, produced by pancreatic α-cells during fasting conditions, when it induces hepatic glucose production through the activation of glycogenolysis and, with more prolonged fasting, also stimulation of gluconeogenesis.…”

Section: 2mentioning

confidence: 99%

Complications of Acute and Chronic Hyperglycemia

Marcovecchio¹

2017

US Endocrinology

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Hyperglycemia is due to a dysregulation in the complex mechanisms implicated in glucose homeostasis. Chronic hyperglycemia, as measured by hemoglobin A1c (HbA1c), is a key risk factor for the development of microvascular and macrovascular complications, which in turn negatively influence the prognosis of patients with diabetes. Several studies have shown that acute hyperglycemia can add to the effect of chronic hyperglycemia in inducing tissue damage. Acute hyperglycemia can manifest as high fasting plasma glucose (FPG) or high postprandial plasma glucose (PPG) and can activate the same metabolic and hemodynamic pathways as chronic hyperglycemia. Glucose variability, as expressed by the intraday glucose fluctuations from peaks to nadirs, is another important parameter, which has emerged as an HbA1c-independent risk factor for the development of vascular complications, mainly in the context of type 2 diabetes. Treatments able to decrease HbA1c have been associated with positive effects in terms of reducing risk for the development and progression of complications. Further studies are required to clarify the impact of strategies more specifically targeting components of acute hyperglycemia, to improve outcomes in patients with diabetes. KeywordsHyperglycemia, complications, vascular, acute, chronic Disclosure: M Loredana Marcovecchio has nothing to disclose in relation to this article. No funding was received in the publication of this article. This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.Authorship: Thel named author meets the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, takes responsibility for the integrity of the work as a whole, and has given final approval to the version to be published.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. From glucose homeostasis to hyperglycemiaGlucose homeostasis is maintained by a complex neurohormonal system, which modulates peripheral glucose uptake, hepatic glucose production, and exogenous glucose utilization following food ingestion.1,2 This allows the maintenance of plasma glucose concentrations within normal range, with average values of around 90 mg/dl throughout a 24-hour period, postmeal concentration below 140 mg/dl, and minimal values, such as those after moderate fasting or exercise, above 55 mg/dl. 1,2Hormones implicated in glucose regulation include insulin, glucagon, amylin, glucagon-like petide-1 (GLP-1), glucose-dependent insulinotropic peptide, epinephrine, cortisol, and growth hormone. These hormones act on several target tissues, including muscle, liver, adipocyte, and brain to regulate glucose levels. 3Insulin is a key glucoregulatory hormone, produced by pancreatic β-cells, whose levels are low durin...

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“…The basal-bolus insulin regimens usually consist of basal analog insulin, such as Lantus (glargine) or Levemir (detemir), which are designed to distribute a fairly constant level of insulin over a 24-hour period. Basal insulin is prescribed toward achievement of glucose homeostasis directed at the liver's continuous release of endogenous glucose into the bloodstream [10]. The bolus of rapid-acting analog insulin is delivered at mealtimes and is prescribed to process the food consumed.…”

Section: Scheduled Basal and Prandial Insulin Bolus Dosingmentioning

confidence: 99%

The Next Step for Inpatient Insulin Dosing: Using Carbohydrate to Insulin Ratios

Norman¹

2015

JDMDC

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Glucose Metabolism and Regulation: Beyond Insulin and Glucagon

Cited by 472 publications

References 72 publications

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism

Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism

Complications of Acute and Chronic Hyperglycemia

The Next Step for Inpatient Insulin Dosing: Using Carbohydrate to Insulin Ratios

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