scholarly journals Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight-Loss

2021 ◽  
Author(s):  
Rachel Ben-Haroush Schyr ◽  
Abbas Al-Kurd ◽  
Botros Moalem ◽  
Anna Permyakova ◽  
Hadar Israeli ◽  
...  
Keyword(s):  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Hepatic Steatosis ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Insulin Clearance ◽  
Insulin Metabolism ◽  
Insulin Levels ◽  
Hepatic Glucose ◽  
Hepatic Insulin Clearance

Bariatric surgeries induce weight loss which is associated with an improvement in hepatic steatosis and reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight-loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet, and compared them to diet and weight-matched sham-operated mice (WMS). 40 days after surgery, VSG-operated mice displayed lesser hepatic steatosis compared to WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through weight-loss and diet-independent mechanisms.

scholarly journals Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight-Loss

2021 ◽  
Author(s):  
Rachel Ben-Haroush Schyr ◽  
Abbas Al-Kurd ◽  
Botros Moalem ◽  
Anna Permyakova ◽  
Hadar Israeli ◽  
...  
Keyword(s):  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Hepatic Steatosis ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Insulin Clearance ◽  
Insulin Metabolism ◽  
Insulin Levels ◽  
Hepatic Glucose ◽  
Hepatic Insulin Clearance

Bariatric surgeries induce weight loss which is associated with an improvement in hepatic steatosis and reduction in hepatic glucose production. It is not clear whether these outcomes are entirely due to weight-loss, or whether the new anatomy imposed by the surgery contributes to the improvement in the metabolic function of the liver. We performed vertical sleeve gastrectomy (VSG) on obese mice provided with a high-fat high-sucrose diet, and compared them to diet and weight-matched sham-operated mice (WMS). 40 days after surgery, VSG-operated mice displayed lesser hepatic steatosis compared to WMS. By measuring the fasting glucose and insulin levels in the blood vessels feeding and draining the liver we showed directly that hepatic glucose production was suppressed after VSG. Insulin levels were elevated in the portal vein, and hepatic insulin clearance was elevated in VSG-operated mice. The hepatic expression of genes associated with insulin clearance was upregulated. We repeated the experiment in lean mice and observed that portal insulin and glucagon are elevated, but only insulin clearance is increased in VSG-operated mice. In conclusion, direct measurement of glucose and insulin in the blood entering and leaving the liver shows that VSG affects glucose and insulin metabolism through weight-loss and diet-independent mechanisms.

scholarly journals Sleeve Gastrectomy Suppresses Hepatic Glucose Production and Increases Hepatic Insulin Clearance Independent of Weight-Loss

Diabetes ◽  
2021 ◽  
pp. db210251
Author(s):  
Rachel Ben-Haroush Schyr ◽  
Abbas Al-Kurd ◽  
Botros Moalem ◽  
Anna Permyakova ◽  
Hadar Israeli ◽  
...  
Keyword(s):  
Weight Loss ◽  
Sleeve Gastrectomy ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Insulin Clearance ◽  
Hepatic Glucose ◽  
Hepatic Insulin Clearance

Nasal insulin administration does not affect hepatic glucose production at systemic fasting insulin levels

2019 ◽  
Vol 21 (4) ◽  
pp. 993-1000
Author(s):  
Peter Plomgaard ◽  
Jakob S. Hansen ◽  
Bodil Ingerslev ◽  
Jens O. Clemmesen ◽  
Niels H. Secher ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Fasting Insulin ◽  
Insulin Administration ◽  
Insulin Levels ◽  
Hepatic Glucose

Effects of differing insulin levels on response to equivalent hypoglycemia in conscious dogs

1992 ◽  
Vol 263 (4) ◽  
pp. E688-E695 ◽  
Author(s):  
S. N. Davis ◽  
R. Dobbins ◽  
C. Tarumi ◽  
C. Colburn ◽  
D. Neal ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Conscious Dogs ◽  
High Dose ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Hepatic Glucose ◽  
High Insulin ◽  
Arterial Insulin

The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia. Insulin was infused intraportally into normal 18-h-fasted conscious dogs at 2 (low, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during the high dose to maintain plasma glucose similar to low (50 +/- 1 mg/dl). Despite similar plasma glucose levels, epinephrine (2,589 +/- 260, 806 +/- 180 pg/ml), norepinephrine (535 +/- 60, 303 +/- 55 pg/ml), cortisol (12.1 +/- 1.5, 5.8 +/- 1.2 micrograms/dl), and pancreatic polypeptide (1,198 +/- 150, 598 +/- 250 pg/ml) were all increased in the presence of high-dose insulin (P < 0.05). Glucagon levels were similar during both insulin infusions. Hepatic glucose production, measured with [3-3H]-glucose, rose from 2.6 +/- 0.2 to 4.7 +/- 0.3 mg.kg-1.min-1 in response to high insulin (P < 0.01) but remained unchanged, 3.0 +/- 0.5 mg.kg-1.min-1, during low-dose infusions. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. By the final hour of the high-dose euglycemic clamps, cortisol (2.4 +/- 0.4 to 4.8 +/- 0.8 micrograms/dl) and norepinephrine (125 +/- 34 to 278 +/- 60 pg/ml) had increased (P < 0.05) compared with baseline. Plasma epinephrine levels remained unchanged during both series of euglycemic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin action on the liver in vivo

2007 ◽  
Vol 35 (5) ◽  
pp. 1171-1174 ◽  
Author(s):  
A.D. Cherrington ◽  
M.C. Moore ◽  
D.K. Sindelar ◽  
D.S. Edgerton
Keyword(s):  
Insulin Action ◽  
Direct Action ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Inhibitory Effect ◽  
Fat Cell ◽  
Insulin Levels ◽  
Hepatic Glucose ◽  
Potent Inhibitory Effect

Insulin has a potent inhibitory effect on hepatic glucose production by direct action at hepatic receptors. The hormone also inhibits glucose production by suppressing both lipolysis in the fat cell and secretion of glucagon by the α-cell. Neural sensing of insulin levels appears to participate in control of hepatic glucose production in rodents, but a role for brain insulin sensing has not been documented in dogs or humans. The primary effect of insulin on the liver is its direct action.

scholarly journals NSAID-Induced Enteropathy Affects Regulation of Hepatic Glucose Production by Decreasing GLP-1 Secretion

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 120
Author(s):  
Hussein Herz ◽  
Yang Song ◽  
Yuanchao Ye ◽  
Liping Tian ◽  
Benjamin Linden ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Treated Group ◽  
Endogenous Glucose Production ◽  
Glucose Disposal ◽  
Control Group ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Insulin Levels ◽  
Hepatic Glucose

Background/Aim: Given their widespread use and their notorious effects on the lining of gut cells, including the enteroendocrine cells, we explored if chronic exposure to non-steroidal anti-inflammatory drugs (NSAIDs) affects metabolic balance in a mouse model of NSAID-induced enteropathy. Method: We administered variable NSAIDs to C57Blk/6J mice through intragastric gavage and measured their energy balance, glucose hemostasis, and GLP-1 levels. We treated them with Exendin-9 and Exendin-4 and ran a euglycemic-hyperinsulinemic clamp. Results: Chronic administration of multiple NSAIDs to C57Blk/6J mice induces ileal ulcerations and weight loss in animals consuming a high-fat diet. Despite losing weight, NSAID-treated mice exhibit no improvement in their glucose tolerance. Furthermore, glucose-stimulated (glucagon-like peptide -1) GLP-1 is significantly attenuated in the NSAID-treated groups. In addition, Exendin-9—a GLP-1 receptor antagonist—worsens glucose tolerance in the control group but not in the NSAID-treated group. Finally, the hyper-insulinemic euglycemic clamp study shows that endogenous glucose production, total glucose disposal, and their associated insulin levels were similar among an ibuprofen-treated group and its control. Exendin-4, a GLP-1 receptor agonist, reduces insulin levels in the ibuprofen group compared to their controls for the same glucose exchange rates. Conclusions: Chronic NSAID use can induce small intestinal ulcerations, which can affect intestinal GLP-1 production, hepatic insulin sensitivity, and consequently, hepatic glucose production.

Peripheral effects of insulin dominate suppression of fasting hepatic glucose production

1990 ◽  
Vol 258 (6) ◽  
pp. E1020-E1032 ◽  
Author(s):  
M. Ader ◽  
R. N. Bergman
Keyword(s):  
Specific Activity ◽  
Hepatic Glucose Production ◽  
Insulin Dose ◽  
Glucose Production ◽  
Insulin Levels ◽  
Exogenous Glucose ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Gluconeogenic Substrates ◽  
Intraportal Infusion

Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release of gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. Insulin was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) or systemically at half the intraportal rate (0.025, 0.10, 0.20, 0.50, 0.70, and/or 1.5 mU.min-1.kg-1; protocol II). Exogenous glucose infused during clamps was labeled with 3-[3H]glucose (2 microCi/g) to prevent a fall in plasma specific activity (P greater than 0.2) that may have contributed to previous underestimations of hepatic glucose output (HGO). Portal insulins were up to threefold higher during intraportal infusion, but peripheral insulin levels were not different between the intraportal and systemic protocols [7 +/- 5 vs. 9 +/- 1, 12 +/- 4 vs. 13 +/- 6, 16 +/- 3 vs. 27 +/- 5, 70 +/- 23 vs. 48 +/- 8, 83 +/- 3 vs. 86 +/- 21, and 128 vs. 120 +/- 14 microU/ml for paired insulin doses; P greater than 0.06 by analysis of variance (ANOVA)]. Despite higher portal insulin levels in protocol I, HGO suppression was equivalent in the two protocols when systemic insulin was matched, from 3.3 +/- 0.1 to near-total suppression at 0.3 mg.min-1.kg-1 at the highest insulin infusion rate (3.0 mU.min-1.kg-1; P less than 0.0001) with intraportal insulin, from 2.9 +/- 0.8 to -0.8 +/- 0.2 mg.min-1.kg-1 in protocol II (P less than 0.001). Suppression of HGO was similar at matched systemic insulin, regardless of portal insulin, suggesting the primacy of insulin's action on the periphery in its restraint of hepatic glucose production.

Absorption and disposition of a glucose load in the conscious dog

1982 ◽  
Vol 242 (6) ◽  
pp. E398-E406 ◽  
Author(s):  
N. N. Abumrad ◽  
A. D. Cherrington ◽  
P. E. Williams ◽  
W. W. Lacy ◽  
D. Rabin
Keyword(s):  
Hepatic Glucose Production ◽  
Control Period ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Load ◽  
Insulin Levels ◽  
Glucose Ingestion ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Arterial Glucose

The quantitative disposition of an intragastrically administered glucose load was studied in eight conscious 18-h fasted dogs using isotopic and arteriovenous (A-V) techniques. During the control period, the gut utilized 25% of the basal net hepatic glucose output (2.8 +/- 0.2 mg.kg-1.min-1). After glucose ingestion, 80% of the load was absorbed as glucose, 11% was converted across the gut to lactate and alanine, and 4% was oxidized to CO2. Two percent of the load remained in the gut 4 h after glucose administration and 3% was unaccounted for. During the absorptive period, net hepatic glucose balance (NHGB) varied considerably (mean range = output of 1.8 to uptake of 9.1 mg.kg-1.min-1), while endogenous hepatic glucose production (Ra hp) showed a consistent 80% suppression. The total net hepatic glucose uptake during the absorptive period (150 +/- 10 min) accounted for the disposal of 24 +/- 10% of the ingested load, and the amount of glucose escaping the splanchnic bed was 40 +/- 3%. Overall NHGB correlated positively with basal arterial glucose and insulin levels and negatively with basal arterial glycerol and FFA and with peak absorptive arterial glucose and insulin levels. These data suggest that the hepatic response to an ingested glucose load depends in part on the degree of metabolic fast of the animal at the time of glucose ingestion; the latter may be a major determinant of the roles played by the tissues in glucose disposal.

scholarly journals Evidence of a Role for Insulin-Like Growth Factor Binding Protein (IGFBP)-3 in Metabolic Regulation

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5741-5750 ◽  
Author(s):  
P. M. Yamada ◽  
H. H. Mehta ◽  
D. Hwang ◽  
K. P. Roos ◽  
A. L. Hevener ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Hepatic Steatosis ◽  
Metabolic Regulation ◽  
Binding Protein ◽  
Hepatic Glucose Production ◽  
Fasting Blood Glucose ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Hepatic Glucose ◽  
Igfbp 3

IGF-binding protein (IGFBP)-3 is a metabolic regulator that has been shown to inhibit insulin-stimulated glucose uptake in murine models. This finding contrasts with epidemiological evidence of decreased serum IGFBP-3 in patients with type 2 diabetes. The purpose of this study was to clarify the role of IGFBP-3 in metabolism. Four-week-old male IGFBP-3−/− and control mice were subjected to a high-fat diet (HFD) for 12 wk. IGFBP-3−/− mice were heavier before the initiation of HFD and at the end of the study period. Resting metabolic rate was significantly decreased in knockout mice; however, respiratory exchange ratio was not significantly different. Fasting blood glucose and insulin levels were significantly elevated in IGFBP-3−/− mice. However, IGFBP-3−/− mice had relatively normal glucose tolerance because the relative glucose excursion over time was not different between the groups. During hyperinsulinemic clamps, IGFBP-3−/− mice had increased basal hepatic glucose production, but after insulin stimulation, no differences in hepatic glucose production were observed. A second cohort of older IGFBP-3−/− mice on HFD displayed unexpected evidence of hepatic steatosis. In summary, glucose tolerance and clamp testing indicate that IGFBP-3−/− mice preserve insulin sensitivity despite evidence of increased basal glucose turnover and hepatic steatosis. We provide evidence that genetic deletion of IGFBP-3 modulates hepatic carbohydrate and lipid metabolism.

scholarly journals Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during euglycemia

2006 ◽  
Vol 190 (3) ◽  
pp. 695-702 ◽  
Author(s):  
Neehar Gupta ◽  
Edward Park ◽  
Harmanjit Sandhu ◽  
Tracy Goh ◽  
Vaja Tchipashvili ◽  
...  
Keyword(s):  
Direct Effect ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Direct Effects ◽  
Direct Inhibition ◽  
Insulin Levels ◽  
Hepatic Glucose ◽  
Per Se ◽  
Diabetic Dogs ◽  
Insulin Replacement

Insulin suppresses glucose production (GP) via both extrahepatic (indirect) and hepatic (direct) effects. We have shown that the direct effect, undetectable in moderately hyperglycemic diabetic dogs, is restored by insulin-induced euglycemia. The first aim of the present study was to determine whether euglycemia per se, and not the excess insulin needed to obtain it, restores the direct effect of insulin on GP. Basal insulin was given portally in depancreatized dogs to attain only moderate hyperglycemia, then an additional insulin was given portally or peripherally to match the peripheral insulin levels and thus to obtain a greater hepatic insulinization with portal delivery. Plasma glucose was allowed to fall to euglycemia before a euglycemic clamp was performed. During euglycemia, there was a tendency (P=0.075) for greater suppression of GP by portal than peripheral insulin. Also, there was a significantly different effect of time (P=0.01) on GP in the two groups, with greater suppression over time in the portal group. The second aim was to test the hypothesis that because of inadequate hepatic insulinization and consequent lack of direct inhibition of GP, peripheral insulin replacement requires peripheral hyperinsulinemia to achieve euglycemia. Portal or peripheral insulin was given to achieve euglycemia and basal GP, and insulin levels were measured. More peripheral insulinemia was required with peripheral than portal insulin replacement to maintain similar euglycemia and GP. Our conclusions are as follows: (1) euglycemia per se is sufficient to acutely restore the direct effect of insulin on GP and (2) at euglycemia, peripheral replacement of insulin, as in insulin-treated diabetes, results in peripheral hyperinsulinemia but unchanged basal GP.

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