Autoregulation of hepatic glucose production

Moore, Mary Courtney; Connolly, Cynthia C.; Cherrington, Alan D.

doi:10.1530/eje.0.1380240

Cited by 102 publications

(76 citation statements)

References 52 publications

(77 reference statements)

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“…32,33 On the other hand, hyperglycaemia is also known to contribute to the decline of hepatic glucose production, although with mechanisms still poorly understood. 34 Whether the more pronounced decline in plasma amino acids observed during period A of our study, as compared with the basal period, was entirely due to hyperinsulinaemia or to the combination of hyperinsulinaemia and hyperglycaemia cannot be easily understood. Anyway, the disappearance of amino acids from plasma was similar in obese subjects and in controls, suggesting an intact amino acid metabolism in obesity in this experimental condition.…”

Section: Discussionmentioning

confidence: 71%

Effects of hyperglycaemia and hyperinsulinaemia on plasma amino acid levels in obese subjects with normal glucose tolerance

et al. 2000

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OBJECTIVE: To investigate the effects of hyperglycaemia and hyperinsulinaemia on amino acid disposal in human obesity. DESIGN: Four sequential experimental conditions: (1) overnight fasting; (2) hyperglycaemia with hyperinsulinaemia (2 h hyperglycaemic clamp at 11 mmolal); (3) hyperglycaemia with basal insulin (1 h hyperglycaemic clamp during somatostatin infusion), (4) hyperglycaemia with resuming hyperinsulinaemia (1 h hyperglycaemic clamp after somatostatin discontinuation). SUBJECTS: Seven non-obese and seven obese non-diabetic, normo-insulinaemic subjects. MEASUREMENTS: Glucose infused to maintain steady-state hyperglycaemia. Plasma insulin, glucagon, free fatty acid and amino acid concentrations in the last 20 min of the four experimental conditions. Net rates of plasma amino acid disappearance and appearance (m mmolal per hour), calculated as the slopes of the regression of amino acid concentration on time. RESULTS: The amount of glucose infused to maintain hyperglycaemia was reduced by nearly 50% in obese subjects. During hyperinsulinaemia, FFA suppression was lower in obese subjects. In all experimental conditions plasma amino acid levels were slightly, non-signi®cantly higher in obese than in non-obese subjects. In both groups plasma amino acids decreased slightly with ongoing fasting, decreased remarkably during hyperglycaemia ± hyperinsulinaemia, rose promptly when insulin concentration was suppressed by somatostatin infusion, and declined again after somatostatin discontinuation. Also the time-course of plasma branched-chain amino acids, which paralleled that of total amino acids, was similar in the two groups. The net rates of amino acid disappearance from plasma did not differ in obese and non-obese subjects both at fasting and during hyperglycaemia ± hyperinsulinaemia. Also plasma amino acid appearance during hyperglycaemia with basal insulin was not different in the two groups. CONCLUSION: The net traf®c of amino acids to and from plasma in relation to insulin drive and prevailing glucose is not impaired in obese subjects with normal glucose tolerance, in spite of a decreased insulin sensitivity of glucose and lipid metabolism.

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Section: Discussionmentioning

confidence: 71%

Effects of hyperglycaemia and hyperinsulinaemia on plasma amino acid levels in obese subjects with normal glucose tolerance

et al. 2000

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“…Glucagon comes into play early in the hierarchy of glucose counterregulatory responses and facilitates glycemic recovery, even in the face of epinephrine deficiency or ␣-and ␤-adrenergic blockade (26). Other possibilities, probably less important or acting later in the counterregulatory hierarchy than glucagon, include enhanced endogenous glucose production secondary to neural activation of liver tissues, enhanced glucose output as a direct inverse effect of circulating glucose concentration (autoregulation), or increased circulating substrates, such as free fatty acids, that can decrease glucose utilization as well as increase hepatic output (27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

Effect of Acute and Antecedent Hypoglycemia on Sympathetic Neural Activity and Catecholamine Responsiveness in Normal Rats

Sivitz

Herlein

Morgan³

et al. 2001

Diabetes

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Adrenergic responsiveness to acute hypoglycemia is impaired after prior episodes of hypoglycemia. Although circulating epinephrine responses are blunted, associated alterations in adrenal sympathetic nerve activity (SNA) have not been reported. We examined adrenal nerve traffic in normal conscious rats exposed to acute insulin-induced hypoglycemia compared with insulin with (clamped) euglycemia. We also examined adrenal SNA and catecholamine responses to insulin-induced hypoglycemia in normal conscious rats after two antecedent episodes of hypoglycemia (days ؊2 and ؊1) compared with prior episodes of sham treatment. Acute insulin-induced hypoglycemia increased adrenal sympathetic nerve traffic compared with insulin administration with clamped euglycemia (165 ؎ 12 vs. 118 ؎ 21 spikes/s [P < 0.05]; or to 138 ؎ 8 vs. 114 ؎ 10% of baseline [P < 0.05]). In additional experiments, 2 days of antecedent hypoglycemia (days -2 and -1) compared with sham treatment significantly enhanced baseline adrenal SNA measured immediately before subsequent acute hypoglycemia on day 0 (180 ؎ 11 vs. 130 ؎ 12 spikes/s, respectively; P < 0.005) and during subsequent acute hypoglycemia (229 ؎ 17 vs. 171 ؎ 16 spikes/s; P < 0.05). However, antecedent hypoglycemia resulted in a nonsignificant reduction in hypoglycemic responsiveness of adrenal SNA when expressed as percent increase over baseline (127 ؎ 5% vs. 140 ؎ 14% of baseline). Antecedent hypoglycemia, compared with sham treatment, resulted in diminished epinephrine responsiveness to subsequent hypoglycemia. Norepinephrine responses to hypoglycemia were not significantly altered by antecedent hypoglycemia. In summary, prior hypoglycemia in normal rats increased adrenal sympathetic tone, but impaired epinephrine responsiveness to acute hypoglycemia. Hence, these data raise the intriguing possibility that increased sympathetic tone resulting from antecedent hypoglycemia downregulates subsequent epinephrine responsiveness to hypoglycemia. Alternatively, it is possible that the decrease in epinephrine responsiveness after antecedent hypoglycemia could be the result of reduced adrenal sympathetic nerve responsiveness. Diabetes 50:1119 -1125, 2001 I mpaired hypoglycemic counterregulation and hypoglycemia unawareness are well-recognized complications of long-standing diabetes (1,2). Hypoglycemia unawareness has also been observed as a reversible consequence of transient prior hypoglycemic events (3-5) and has been observed even in individuals without diabetes (6). However, the pathophysiology of hypoglycemic counterregulation and hypoglycemia unawareness is still unclear. Although much has been learned of catecholamine and other hormonal responses to hypoglycemia, the role of sympathetic neural activity per se to adrenal and other tissues has received only limited study.Peripheral sympathetic nerve activity (SNA) originating in hypothalamic centers may be important in the counterregulatory response to hypoglycemia. Hoffman et al. (7) found that skeletal muscle SNA in type 1 diabetic and nondia...

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“…This assumption is further supported by the lack of difference in plasma glucagon and the glucagon to insulin ratio between groups. Therefore, reduced eGP might be a result of autoregulation (Danfaer, 1994;Brockman, 2005), although the regulation of eGP by glucokinase activity may be less pronounced in ruminants (Moore et al, 1998;Tappy et al, 2000).…”

Section: Cla Effects On Glucose Metabolismmentioning

confidence: 99%

Supplementation of conjugated linoleic acid in dairy cows reduces endogenous glucose production during early lactation

Hötger

Hammon

Weber

et al. 2013

Journal of Dairy Science

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Trans-10,cis-12 conjugated linoleic acid (CLA) supplementation causes milk fat depression in dairy cows, but CLA effects on glucose metabolism are not clear. The objective of the study was to investigate glucose metabolism, especially endogenous glucose production (eGP) and glucose oxidation (GOx), as well as hepatic genes involved in endogenous glucose production in Holstein cows supplemented either with 50 g of rumen-protected CLA (9% trans-10,cis-12 and 10% cis-9,trans-11; CLA; n = 10) or 50 g of control fat (24% C18:2; Ctrl; n = 10) from wk 2 before parturition to wk 9 of lactation. Animal performance data were recorded and blood metabolites and hormones were taken weekly from 2 wk before to 12 wk after parturition. During wk 3 and 9 after parturition, glucose tolerance tests were performed and eGP and GOx were measured by [U-13 C] glucose infusion. Liver biopsies were taken at the same time to measure total fat and glycogen concentrations and gene expression of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and carnitine palmitoyl-transferase 1. Conjugated linoleic acid feeding reduced milk fat, but increased milk lactose output; milk yield was higher starting 5 wk after parturition in CLA-fed cows than in Ctrl-fed cows. Energy balance was more negative during CLA supplementation, and plasma concentrations of glucose were higher immediately after calving in CLAfed cows. Conjugated linoleic acid supplementation did not affect insulin release during glucose tolerance tests, but reduced eGP in wk 3, and eGP and GOx increased with time after parturition. Hepatic gene expression of cytosolic phosphoenolpyruvate carboxykinase tended to be lower in CLA-fed cows than in Ctrl-fed cows. In spite of lower eGP in CLA-fed cows, lactose output and plasma glucose concentrations were greater in CLA-fed cows than in Ctrl-fed cows. This suggests a CLA-related glucose sparing effect most likely due to lower glucose utilization for milk fat synthesis and probably because of a more efficient whole-body energy utilization in CLA-fed cows.

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Autoregulation of hepatic glucose production

Cited by 102 publications

References 52 publications

Effects of hyperglycaemia and hyperinsulinaemia on plasma amino acid levels in obese subjects with normal glucose tolerance

Effects of hyperglycaemia and hyperinsulinaemia on plasma amino acid levels in obese subjects with normal glucose tolerance

Effect of Acute and Antecedent Hypoglycemia on Sympathetic Neural Activity and Catecholamine Responsiveness in Normal Rats

Supplementation of conjugated linoleic acid in dairy cows reduces endogenous glucose production during early lactation

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