Insulin stimulates epinephrine release under euglycemic conditions in humans

Tack, Cees J.; Lenders, J. W. M.; Willemsen, Jacques J.; Druten, J.A.M. van; Thien, Theo; Lutterman, J.A.; Smits, Paul

doi:10.1016/s0026-0495(98)90251-7

Cited by 26 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whether the differences in route of insulin delivery contributed to this difference is uncertain. However, systemically administered insulin is known to increase plasma catecholamines (29,30) and cardiac output.…”

Section: Discussionmentioning

confidence: 99%

Obesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle

et al. 2006

View full text Add to dashboard Cite

We have previously shown that skeletal muscle capillaries are rapidly recruited by physiological doses of insulin in both humans and animals. This facilitates glucose and insulin delivery to muscle, thus augmenting glucose uptake. In obese rats, both insulin-mediated microvascular recruitment and glucose uptake are diminished; however, this action of insulin has not been studied in obese humans. Here we used contrast ultrasound to measure microvascular blood volume (MBV) (an index of microvascular recruitment) in the forearm flexor muscles of lean and obese adults before and after a 120-min euglycemic-hyperinsulinemic (1 mU ⅐ min ؊1 ⅐ kg ؊1 ) clamp. We also measured brachial artery flow, fasting lipid profile, and anthropomorphic variables. Fasting plasma glucose (5.4 ؎ 0.1 vs. 5.1 ؎ 0.1 mmol/l, P ‫؍‬ 0.05), insulin (79 ؎ 11 vs. 38 ؎ 6 pmol/l, P ‫؍‬ 0.003), and percent body fat (44 ؎ 2 vs. 25 ؎ 2%, P ‫؍‬ 0.001) were higher in the obese than the lean adults. After 2 h of insulin infusion, whole-body glucose infusion rate was significantly lower in the obese versus lean group (19.3 ؎ 3.2 and 37.4 ؎ 2.6 mol ⅐ min ؊1 ⅐ kg ؊1 respectively, P < 0.001). Compared with baseline, insulin increased MBV in the lean (18.7 ؎ 3.3 to 25.0 ؎ 4.1, P ‫؍‬ 0.019) but not in the obese group (20.4 ؎ 3.6 to 18.8 ؎ 3.8, NS). Insulin increased brachial artery diameter and flow in the lean but not in the obese group. We observed a significant, negative correlation between ⌬MBV and BMI (R ‫؍‬ ؊0.482, P ‫؍‬ 0.027) in response to insulin. In conclusion, obesity eliminated the insulin-stimulated muscle microvascular recruitment and increased brachial artery blood flow seen in lean individuals.

show abstract

Section: Discussionmentioning

confidence: 99%

Obesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle

et al. 2006

View full text Add to dashboard Cite

show abstract

“…This method has the potential disadvantage of being strongly influenced by blood in larger vessels, which may not show the same responses as the microvasculature to vasoactive agents. Furthermore, systemic infusion of high doses of insulin causes secondary changes in systemic and local release of catecholamines, which may themselves induce changes in both blood flow and volume (49,50).…”

Section: Discussionmentioning

confidence: 99%

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

et al. 2001

View full text Add to dashboard Cite

Despite intensive study, the relation between insulin's action on blood flow and glucose metabolism remains unclear. Insulin-induced changes in microvascular perfusion, independent from effects on total blood flow, could be an important variable contributing to insulin's metabolic action. We hypothesized that modest, physiologic increments in plasma insulin concentration alter microvascular perfusion in human skeletal muscle and that these changes can be assessed using contrastenhanced ultrasound (CEU), a validated method for quantifying flow by measurement of microvascular blood volume (MBV) and microvascular flow velocity (MFV). In the first protocol, 10 healthy, fasting adults received insulin (0.05 mU ⅐ kg ؊1 ⅐ min ؊1 ) via a brachial artery for 4 h under euglycemic conditions. At baseline and after insulin infusion, MBV and MFV were measured by CEU during continuous intravenous infusion of albumin microbubbles with intermittent harmonic ultrasound imaging of the forearm deep flexor muscles. In the second protocol, 17 healthy, fasting adults received a 4-h infusion of either insulin (0.1 mU ⅐ kg ؊1 ⅐ min ؊1 , n ‫؍‬ 9) or saline (n ‫؍‬ 8) via a brachial artery. Microvascular volume was assessed in these subjects by an alternate CEU technique using an intra-arterial bolus injection of albumin microbubbles at baseline and after the 4-h infusion. With both protocols, muscle glucose uptake, plasma insulin concentration, and total blood flow to the forearm were measured at each stage. In protocol 2 subjects, tissue extraction of 1-methylxanthine (1-MX) was measured as an index of perfused capillary volume. Caffeine, which produces 1-MX as a metabolite, was administered to these subjects before the study to raise plasma 1-MX levels.In protocol 1 subjects, insulin increased muscle glucose uptake (180%, P < 0.05) and MBV (54%, P < 0.01) and decreased MFV (؊42%, P ‫؍‬ 0.07) in the absence of significant changes in total forearm blood flow. In protocol 2 subjects, insulin increased glucose uptake (220%, P < 0.01) and microvascular volume (45%, P < 0.05) with an associated moderate increase in total forearm blood flow (P < 0.05). Using forearm 1-MX extraction, we observed a trend, though not significant, toward increasing capillary volume in the insulin-treated subjects. In conclusion, modest physiologic increments in plasma insulin concentration increased microvascular blood volume, indicating altered microvascular perfusion consistent with a mechanism of capillary recruitment. The increases in microvascular (capillary) volume (despite unchanged total blood flow) indicate that the relation between insulin's vascular and metabolic actions cannot be fully understood using measurements of bulk blood flow alone.

show abstract

“…Permeability is also increased by increasing endothelin-1 levels, which are stimulated by insulin and an increase in vascular endothelial growth factor and calcium channel blockade caused by the TZD (61-64). Higher catecholamine levels can also increase capillary pressure by their opposing effects on pre-and postcapillary sphincters (65).…”

Section: Use Of Thiazolidinedionesmentioning

confidence: 99%

Heart Failure

2003

View full text Add to dashboard Cite

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of ␤-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. ␤-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with ␤-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation ␤-blocker. Prophylactic utilization of ACE inhibitors and ␤-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.

show abstract

Insulin stimulates epinephrine release under euglycemic conditions in humans

Cited by 26 publications

References 29 publications

Obesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle

Obesity Blunts Insulin-Mediated Microvascular Recruitment in Human Forearm Muscle

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

Heart Failure

Contact Info

Product

Resources

About