Insulin Sensitivity in Skeletal Muscle Regulated by a Hepatic Hormone, HISS

2005 ◽  
Vol 30 (3) ◽  
pp. 304-312 ◽  
Author(s):  
W. Wayne Lautt
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Physiological State ◽  
Nitric Oxide Donor ◽  
Fed State ◽  
Spontaneously Hypertensive ◽  
Parasympathetic Nerves ◽  
Key Words Insulin ◽  
The Impact

The current state of the HISS (hepatic insulin sensitizing substance) hypothesis is briefly outlined. In the postmeal absorptive state, 50-60% of the glucose storage action of insulin is accounted for by the actions of HISS released from the liver and acting on skeletal muscle. Hepatic parasympathetic nerves permissively regulate the ability of a pulse of insulin to release HISS, thereby potentiating the impact of insulin in the fed state. HISS release in response to insulin decreases progressively with fasting to create a physiological state of HISS-dependent insulin resistance. HISS release is regulated by parasympathetic nerves via muscarinic receptors and nitric oxide, and insulin resistance of skeletal muscle produced by hepatic denervation is reversed by intraportal but not intravenous acetylcholine or a nitric oxide donor. It is suggested that HISS-dependent insulin resistance occurs in animal models including sucrose-fed rats, spontaneously hypertensive rats, chronic liver disease, fetal alcohol effect in the adult offspring, and type 2 diabetes. Key words: insulin resistance, RIST, parasympathetic nerves, liver, diabetes

The HISS story overview: a novel hepatic neurohumoral regulation of peripheral insulin sensitivity in health and diabetes

1999 ◽  
Vol 77 (8) ◽  
pp. 553-562 ◽  
Author(s):  
W Wayne Lautt
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Insulin Sensitivity ◽  
Nitric Oxide Donor ◽  
Severe Insulin Resistance ◽  
Parasympathetic Nerves ◽  
Neurohumoral Regulation ◽  
Duct Ligation ◽  
Oxide Synthase

Data are reviewed that are consistent with the following working hypothesis that proposes a novel mechanism regulating insulin sensitivity, which when nonfunctional, leads to severe insulin resistance. Postprandial elevation in insulin levels activates a hepatic parasympathetic reflex release of a putative hepatic insulin-sensitizing substance (HISS), which activates glucose uptake at skeletal muscle. Insulin causes HISS release in fed but not fasted animals. The reflex is mediated by acetylcholine and involves release of nitric oxide in the liver. Interruption of the release of HISS is achieved by surgical denervation of the anterior hepatic nerve plexus, muscarinic receptor blockade, or nitric oxide synthase antagonism and leads to immediate severe insulin resistance. The nitric oxide donor, SIN-1, reverses L-NAME-induced insulin resistance. Denervation-induced insulin resistance is reversed by intraportal but not intravenous administration of acetylcholine or SIN-1. Liver disease is often associated with insulin resistance; the bile duct ligation model of liver disease results in parasympathetic neuropathy and insulin resistance that is reversed by intraportal acetylcholine. Possible relevance of this HISS-dependent control of insulin action to insulin resistance in diabetes, liver disease, and obesity is discussed.Key words: insulin resistance, parasympathetic nerves, liver, obesity, nitric oxide.

The effect of the nitric oxide donor sodium nitroprusside on glucose uptake in human primary skeletal muscle cells

Nitric Oxide ◽  
2009 ◽  
Vol 21 (2) ◽  
pp. 126-131 ◽  
Author(s):  
Darren C. Henstridge ◽  
Brian G. Drew ◽  
Melissa F. Formosa ◽  
Alaina K. Natoli ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Sodium Nitroprusside ◽  
Glucose Uptake ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Nitric Oxide Donor

Reduced insulin receptor signaling in the obese spontaneously hypertensive Koletsky rat

1997 ◽  
Vol 273 (5) ◽  
pp. E1014-E1023 ◽  
Author(s):  
Jacob E. Friedman ◽  
Tatsuya Ishizuka ◽  
Sha Liu ◽  
Craig J. Farrell ◽  
David Bedol ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Tyrosine Phosphorylation ◽  
Glucose Intolerance ◽  
Leptin Receptor ◽  
Spontaneously Hypertensive Rat ◽  
Regulatory Subunit ◽  
Oral Glucose ◽  
Spontaneously Hypertensive

Insulin resistance is associated with both obesity and hypertension. However, the cellular mechanisms of insulin resistance in genetic models of obese-hypertension have not been identified. The objective of the present study was to investigate the effects of genetic obesity on a background of inherited hypertension on initial components of the insulin signal transduction pathway and glucose transport in skeletal muscle and liver. Oral glucose tolerance testing in SHROB demonstrated a sustained postchallenge elevation in plasma glucose at 180 and 240 min compared with lean spontaneously hypertensive rat (SHR) littermates, which is suggestive of glucose intolerance. Fasting plasma insulin levels were elevated 18-fold in SHROB. The rate of insulin-stimulated 3- O-methylglucose transport was reduced 68% in isolated epitrochlearis muscles from the SHROB compared with SHR. Insulin-stimulated tyrosine phosphorylation of the insulin receptor β-subunit and insulin receptor substrate-1 (IRS-1) in intact skeletal muscle of SHROB was reduced by 36 and 23%, respectively, compared with SHR, due primarily to 32 and 60% decreases in insulin receptor and IRS-1 protein expression, respectively. The amounts of p85α regulatory subunit of phosphatidylinositol-3-kinase and GLUT-4 protein were reduced by 28 and 25% in SHROB muscle compared with SHR. In the liver of SHROB, the effect of insulin on tyrosine phosphorylation of IRS-1 was not changed, but insulin receptor phosphorylation was decreased by 41%, compared with SHR, due to a 30% reduction in insulin receptor levels. Our observations suggest that the leptin receptor mutation fak imposed on a hypertensive background results in extreme hyperinsulinemia, glucose intolerance, and decreased expression of postreceptor insulin signaling proteins in skeletal muscle. Despite these changes, hypertension is not exacerbated in SHROB compared with SHR, suggesting these metabolic abnormalities may not contribute to hypertension in this model of Syndrome X.

scholarly journals Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats

Life Sciences ◽  
2018 ◽  
Vol 201 ◽  
pp. 130-140 ◽  
Author(s):  
Simone R. Potje ◽  
Jéssica A. Troiano ◽  
Marcella D. Grando ◽  
Murilo E. Graton ◽  
Roberto S. da Silva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Nitric Oxide Donor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

Hemodynamic actions of insulin

1994 ◽  
Vol 267 (2) ◽  
pp. E187-E202 ◽  
Author(s):  
A. D. Baron
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Pressor Response ◽  
Physiological Role ◽  
Oxide System ◽  
Maximal Response ◽  
Insulin Resistant ◽  
The Right

There is accumulating evidence that insulin has a physiological role to vasodilate skeletal muscle vasculature in humans. This effect occurs in a dose-dependent fashion within a half-maximal response of approximately 40 microU/ml. This vasodilating action is impaired in states of insulin resistance such as obesity, non-insulin-dependent diabetes, and elevated blood pressure. The precise physiological role of insulin-mediated vasodilation is not known. Data indicate that the degree of skeletal muscle perfusion can be an important determinant of insulin-mediated glucose uptake. Therefore, it is possible that insulin-mediated vasodilation is an integral aspect of insulin's overall action to stimulate glucose uptake; thus defective vasodilation could potentially contribute to insulin resistance. In addition, insulin-mediated vasodilation may play a role in the regulation of vascular tone. Data are provided to indicate that the pressor response to systemic norepinephrine infusions is increased in obese insulin-resistant subjects. Moreover, the normal effect of insulin to shift the norepinephrine pressor dose-response curve to the right is impaired in these patients. Therefore, impaired insulin-mediated vasodilation could further contribute to the increased prevalence of hypertension observed in states of insulin resistance. Finally, data are presented to indicate that, via a yet unknown interaction with the endothelium, insulin is able to increase nitric oxide synthesis and release and through this mechanism vasodilate. It is interesting to speculate that states of insulin resistance might also be associated with a defect in insulin's action to modulate the nitric oxide system.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of resistance arteries to reduced PO2 and vasodilators during hypertension and elevated salt intake

1997 ◽  
Vol 273 (2) ◽  
pp. H869-H877 ◽  
Author(s):  
Y. Liu ◽  
K. T. Fredricks ◽  
R. J. Roman ◽  
J. H. Lombard
Keyword(s):  
Skeletal Muscle ◽  
Salt Intake ◽  
High Salt ◽  
Nitric Oxide Donor ◽  
Resistance Arteries ◽  
Hypertensive Rats ◽  
High Salt Diet ◽  
Membrane Function ◽  
Salt Diet ◽  
Spontaneously Hypertensive

This study assessed vasodilator responses in skeletal muscle resistance arteries (100-250 microns) from rats with chronic (4-8 wk) reduced renal mass (RRM) hypertension and normotensive sham-operated controls on a high (4% NaCl; HSSHAM)- or low (0.4% NaCl; LSSHAM)-salt diet. Arteries from RRM hypertensive rats [normal and high-salt diet (HSRRM)] and a separate group of spontaneously hypertensive rats exhibited an impaired dilation in response to reduced PO2 compared with those of their normotensive controls. Prostacyclin release, assessed by radio-immunoassay for 6-ketoprostaglandin F1 alpha, increased significantly in response to reduced PO2, but was unaffected by hypertension or salt intake. Dilator responses to acetylcholine and the prostacyclin analog iloprost were significantly reduced in both HSRRM and HSSHAM compared with LSSHAM rats. Dilation in response to direct activation of adenylate cyclase with forskolin or guanylate cyclase with the nitric oxide donor sodium nitroprusside was not significantly different in HSRRM, HSSHAM, and LSSHAM rats. These results indicate that hypoxic dilation is impaired in skeletal muscle resistance arteries of hypertensive rats and that chronic high-salt diet alone leads to impaired vasodilator responses in resistance arteries of normotensive animals, possibly via abnormalities in membrane function or G protein signaling rather than impaired second-messenger function.

Effect of a Nitric Oxide Donor on Microcirculation of Acutely Denervated Skeletal Muscle during Reperfusion

2002 ◽  
Vol 18 (1) ◽  
pp. 053-060 ◽  
Author(s):  
Chen-Hsi Chou ◽  
Long-En Chen ◽  
Anthony V. Seaber ◽  
James R. Urbaniak
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Donor

Skeletal muscle contraction-induced vasodilator complement production is dependent on stimulus and contraction frequency

2009 ◽  
Vol 297 (1) ◽  
pp. H433-H442 ◽  
Author(s):  
Ashok K. Dua ◽  
Nickesh Dua ◽  
Coral L. Murrant
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Muscle Fibers ◽  
Nitric Oxide Donor ◽  
Contraction Frequency ◽  
Skeletal Muscle Contraction ◽  
Train Duration ◽  
Arteriolar Vasodilation ◽  
40 Hz

To test the hypothesis that the vasodilator complement that produces arteriolar vasodilation during muscle contraction depends on both stimulus and contraction frequency, we stimulated four to five skeletal muscle fibers in the anesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibers. Diameter was measured before, during, and after 2 min of skeletal muscle contraction stimulated over a range of stimulus frequencies [4, 20, and 40 Hz; 15 contractions/min (cpm), 250 ms train duration] and a range of contraction frequencies (6, 15, and 60 cpm; 20 Hz stimulus frequency, 250 ms train duration). Muscle fibers were stimulated in the absence and presence of an inhibitor of adenosine receptors [10−6 M xanthine amine congener (XAC)], an ATP-dependent potassium (K+) channel inhibitor (10−5 M glibenclamide), an inhibitor of a source of K+ by inhibition of voltage-dependent K+ channels [3 × 10−4 M 3,4-diaminopyridine (DAP)], and an inhibitor of nitric oxide synthase [10−6 M NG-nitro-l-arginine methyl ester (l-NAME) + 10−7 S-nitroso- N-acetylpenicillamine (a nitric oxide donor)]. l-NAME inhibited the dilations at all stimulus frequencies and contraction frequencies except 60 cpm. XAC inhibited the dilations at all contraction frequencies and stimulus frequencies except 40 Hz. Glibenclamide inhibited all dilations at all stimulus and contraction frequencies, and DAP did not inhibit dilations at any stimulus frequencies while attenuating dilation at a contraction frequency of 60 cpm only. Our data show that the complement of dilators responsible for the vasodilations induced by skeletal muscle contraction differed depending on the stimulus and contraction frequency; therefore, both are important determinants of the dilators involved in the processes of arteriolar vasodilation associated with active hyperemia.

Insulin resistance of skeletal muscle produced by hepatic parasympathetic interruption

1996 ◽  
Vol 270 (5) ◽  
pp. E858-E863 ◽  
Author(s):  
H. Xie ◽  
W. W. Lautt
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Liver Disease ◽  
Portal Vein ◽  
Combined Treatment ◽  
Random Order ◽  
Acute Effect ◽  
Parasympathetic Nerves ◽  
Before And After ◽  
Insulin Dependent

The objective was to determine the site of insulin resistance produced by intraportal atropine or surgical hepatic denervation. A modified euglycemic clamp was used in fasted cats to test the acute effect of insulin (100 mU/kg) on arteriovenous glucose gradients across the hindlimbs (mainly reflecting skeletal muscle), the guts (all organs draining into the portal vein), and the liver. Responses to insulin were determined before and after hepatic denervation and after 3 mg/kg intraportal atropine. The interventions were done in random order. Responses after either intervention were similar and were not potentiated by the combined treatment. Regional insulin resistance was assessed by comparing the change in glucose gradients in response to insulin before and after treatments. Hepatic and gut responses to insulin were unaltered, but hindlimb responses were significantly impaired after denervation or atropine. We speculate that the hepatic parasympathetic nerves regulate release of a liver-generated factor that selectively controls insulin effectiveness in skeletal muscle. This mechanism may be involved with insulin resistance in non-insulin-dependent diabetes and chronic liver disease.

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