| 1. |
- Fugmann, Andreas, et al.
(författare)
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Blood flow is an important determinant of forearm glucose uptake following a mixed meal
- 2003
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 40:3, s. 113-117
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-mediated vasodilation has been suggested to be of importance for glucose uptake during normoglycemic hyperinsulinemia. If this also is valid after an ordinary mixed meal remains to be evaluated. Forearm blood flow (FBF) and forearm glucose uptake change (evaluated by venous occlusion plethysmography) and glucose arteriovenous differences were evaluated over 120 minutes in 10 healthy volunteers following an ordinary mixed meal (700-900 kcal, 34% of energy from fat). Fasting arterial glucose level was 4.9+/-0.9 mmol/l, and the maximum glucose level was reached 30 minutes after the start of ingestion (6.6+/-0.8 mmol/l, p<0.0001). Plasma insulin levels were increased four-fold. FBF increased rapidly within 20 minutes after the start of ingestion and reached its maximum after 50 minutes (94% higher than baseline level, p<0.01). After 2 hours FBF was still substantially elevated (75% above baseline level, p<0.01). Forearm glucose uptake increased fivefold already after 20 minutes ( p<0.01). During the 2 hours, the increase in FBF contributed to 41% of the forearm glucose uptake ( p<0.05). The present study showed that the increase in FBF seen after an ordinary mixed meal is important for the change in forearm glucose uptake. These results support the view that modulation of limb blood flow is a determinant of glucose uptake.
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| 2. |
- Fugmann, Andreas, et al.
(författare)
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Central and peripheral haemodynamic effects of hyperglycaemia, hyperinsulinaemia, hyperlipidaemia or a mixed meal
- 2003
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 105:6, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P <0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.
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| 3. |
- Fugmann, Andreas
(författare)
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Effects of acute metabolic interventions on hemodynamics, endothelial function and forearm glucose uptake
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hyperinsulinemia is known to augment endothelium-dependent.vasodilation (EDV). If physiological levels of insulin lead to peripheral, vasodilation and if this vasodilation is an independent determinant of skeletal muscle glucose uptake is however under debate. In this thesis the effects of acute metabolic interventions on hemodynamics, endothelial function and forearm glucose uptake were evaluated in healthy subjects. Normoglycemic hyperinsulinemia, as well as ingestion of an ordinary mixed meal, resulted in an increase in forearm blood flow. This increase in flow acted as a late amplifier of insulin mediated limb glucose uptake and contributeed to a substantial part of the total skeletal muscle glucose uptake. In the early events of insulin-mediated glucose uptake, however, an increase in glucose extraction was the main determinant. Acute hyperglycemia, as well as acute hyperlipidemia and ingestion of a mixed meal attenuated endothelium-dependent vasodilation. Endothelium-independent vasodilation was, however, left unaffected. During both hyperglycemia and hyperlipidemia, the attenuation in EDV was normalised by superimposing hyperinsulinemia. The attenuation in EDV after a mixed meal was transient and recovered after 2 hours. The different metabolic interventions induced divergent peripheral and central hemodynamic patterns. Hyperinsulinemia resulted in vasodilation and increased cardiac output similar to that observed after ingestion of a mixed meal. In conclusion, insulin-mediated vasodilation seems to have the ability to amplify insulin-mediated glucose uptake in healthy subjects. All metabolic interventions evaluated, except hyperinsulinemia, resulted in an attenuation of EDV. Hyperinsulinemia, on the other hand, reversed this attenuation. The hemodynamic response seen after ingestion of a mixed meal seems largely to be mediated by hyperinsulinemia.
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| 4. |
- Hänni, Arvo, et al.
(författare)
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Systolic blood pressure alterations during hyperinsulinemia are related to changes in ionized calcium status
- 2001
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Ingår i: American Journal of Hypertension. - 0895-7061 .- 1941-7225. ; 14:11 Pt 1, s. 1106-1111
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A correlation between changes in ionized calcium status and changes in systolic blood pressure (BP) has previously been observed during induced euglycemic hyperinsulinemia in patients with essential hypertension. The objective of this study was to evaluate associations between alterations in ion status and BP changes during euglycemic hyperinsulinemia in healthy normotensive subjects. METHODS: Ion status in plasma and BP were measured before and at the end of euglycemic hyperinsulinemic clamp tests performed in 41 healthy normotensive volunteers. RESULTS: During euglycemic hyperinsulinemia plasma sodium increased by 1% (P < .0001), ionized calcium (iCa) by 5% (P < .0001), and ionized magnesium (iMg) by 4% (P < .01), whereas potassium decreased by 10% (P < .0001). The changes in plasma iCa and iMg correlated significantly to changes in systolic BP (r = -0.38, P < .02; r = -0.32, P < .05, respectively), but the correlation between changes in iMg and changes in systolic BP did not remain significant in a multiple regression model. The glucose infusion rate correlated inversely to the change in iMg (r = -0.39, P < .01). CONCLUSIONS: The group mean systolic BP was unaltered during induced euglycemic hyperinsulinemia in healthy normotensive subjects; however, a more pronounced increase in the circulating iCa concentration was associated with a greater decline in systolic BP, which is in accordance with previous observations in patients with essential hypertension. The group mean diastolic BP was decreased; however, the lowered diastolic BP was not correlated to changes in ion status.
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| 5. |
- Lind, Lars, et al.
(författare)
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Ageing impairs insulin-mediated vasodilatation but not forearm glucose uptake
- 2001
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 31:10, s. 860-864
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is unclear if insulin-mediated vasodilatation is altered by ageing and if this affects insulin-mediated glucose uptake. MATERIAL AND METHODS: A 2-h euglycaemic hyperinsulinaemic clamp (56 mU m(-2) min(-1)) was performed in 10 healthy, nonobese elderly men (70-75 years) and 13 young men (23-28 years). Forearm blood flow (FBF) was measured by venous occlusion plethysmography and forearm glucose uptake was calculated by arterial and venous serum glucose determinations in the forearm. RESULTS: Insulin induced an increase in FBF in the younger men (from 3.9 +/- 1.1 SD to 5.9 +/- 2.2 mL min(-1) 100(-1)mL tissue, P < 0.001), but this insulin-mediated vasodilatation was completely blunted in the elderly subjects. Glucose extraction during the clamp was significantly higher in the elderly subjects (1.2 +/- 0.76 vs. 0.82 +/- 0.37 mmol L(-1) at 120 min, P < 0.01), resulting in a similar forearm glucose uptake in the two groups. On the other hand, whole-body glucose uptake was significantly decreased in the elderly subjects (5.3 +/- 1.8 vs. 8.0 +/- 1.1 mg kg(-1) min(-1), P < 0.001). CONCLUSION: The present study showed that the ability of insulin to induce vasodilatation is blunted in the forearm in healthy, nonobese elderly subjects. However, the elderly compensate for this impairment with an increased glucose extraction from arterial blood to maintain an unaltered forearm glucose uptake.
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| 6. |
- Lind, Lars, et al.
(författare)
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Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated vasodilatation, is enhanced in young females compared with males
- 2002
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 102:2, s. 241-246
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Tidskriftsartikel (refereegranskat)abstract
- In order to evaluate possible differences between men and women with regard to the ability of insulin to induce vasodilatation, promote glucose uptake and enhance endothelium-dependent vasodilatation, 12 young (22-28 years), non-obese women and 15 corresponding males were subjected to 2 h of euglycaemic hyperinsulinaemia (insulin infusion rate of 56 m-units x min(-1) x m(-2)). Forearm blood flow was measured by venous occlusion plethysmography. Endothelium-dependent vasodilatation was evaluated by the local intra-arterial infusion of methacholine into the brachial artery (2-4 microg/min). The cardiac index was measured by thoracic bioimpedance. A 2 h period of hyperinsulinaemia increased the plasma insulin concentration to a similar degree in both sexes (females, 84 +/- 8.8 m-units/l; males, 87 +/- 7.5 m-units/l), but induced a more marked increase in forearm blood flow in females than in males (+104 +/- 67% and +52 +/- 30% respectively; P<0.01; 95% confidence interval for difference 11-94%). Furthermore, a significant decrease in total peripheral resistance (-20 +/- 6.9%; P<0.01) and an increase in cardiac index (+23 +/- 13%; P<0.01) were seen in women only (P<0.05 compared with men). Blood pressure and heart rate were not altered in either sex. Whole-body insulin-mediated glucose uptake and forearm glucose uptake did not differ between the sexes, and the ability of insulin to enhance endothelium-dependent vasodilatation (+19%; P<0.01) was similar in men and women. In conclusion, the present study shows that the ability of insulin to cause vasodilatation was greater in non-obese young women compared with men. However, no differences between the sexes were seen with regard to insulin-mediated glucose uptake and the ability of insulin to enhance endothelium-dependent vasodilatation.
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| 7. |
- Lind, Lars, et al.
(författare)
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The impairment in endothelial function induced by non-esterified fattyacids can be reversed by insulin
- 2000
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 99:3, s. 169-174
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Tidskriftsartikel (refereegranskat)abstract
- Dyslipidaemia, with elevations of circulating triacylglycerols (triglycerides) and non-esterified (free) fatty acids, and hyperinsulinaemia are often found in the same subjects, the so-called 'insulin resistance syndrome'. The present study aims to investigate how elevated levels of non-esterified fatty acids, hyperinsulinaemia and the combination of these factors affects endothelium-dependent vasodilatation (EDV). Ten volunteers were examined on two occasions. Intralipid (plus heparin) or saline (0.9% NaCl) was infused for 4 h. During the final 2 h, euglycaemic hyperinsulinaemia (80+/-4 m-units/l) was imposed. EDV and endothelium-independent vasodilatation were evaluated in the forearm by local intra-arterial infusion of methacholine or sodium nitroprusside at baseline and after 2 and 4 h. Forearm blood flow was measured by venous occlusion plethysmography. Lipid oxidation was determined by measuring plasma malondialdehyde levels. Infusion of Intralipid plus heparin increased the concentration of non-esterified fatty acids to 2.6+/-1.2 mmol/l and decreased EDV from 27.6+/-8.7 to 21.0+/-5.7 ml x min(-1) x 100 ml(-1) tissue (P < 0.01). This effect was completely reversed by hyperinsulinaemia (P < 0.01). Hyperinsulinaemia alone increased EDV (to 30.4+/-9.5 ml x min(-1) x 100 ml(-1) tissue; P < 0.01), while endothelium-independent vasodilatation was unaltered by the interventions. Infusion of Intralipid plus heparin increased malondialdehyde levels from 0.67+/-0.22 to 1.2+/-0.37 micromol/l (P < 0.001), while hyperinsulinaemiadid not change the malondialdehyde level. In conclusion, an acute increase in serum levels of non-esterified fatty acids increased lipid oxidation and decreased EDV. The effect on EDV of non-esterified fatty acids could be reversed by hyperinsulinaemia.
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| 8. |
- Sarabi, Mahziar, et al.
(författare)
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An ordinary mixed meal transiently impairs endothelium-dependent vasodilation in healthy subjects
- 2001
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772 .- 1365-201X. ; 172:2, s. 107-113
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Tidskriftsartikel (refereegranskat)abstract
- This study was designed to evaluate the effects of an ordinary mixed meal on endothelium-dependent vasodilation. Ten young healthy volunteers were given a mixed meal (minced meat sauce with rice, 900 kcal, 34% of the energy content was fat). In the fasting state, at 60 and 120 min after the start of the meal, endothelium-dependent vasodilation and endothelium-independent vasodilation were evaluated by local infusion of metacholine (4 microg min (-1)) and sodium nitroprusside (10 microg min (-1)) in the brachial artery. Blood flow in the forearm was measured using venous occlusion plethysmography. Endothelium-dependent vasodilation decreased from 15.4 +/- 3.3 (mean +/- SD) at fasting to 13.7 +/- 3.5 mL min (-1) (100 mL tissue)-1 (P < 0.01) 60 min after feeding, but had returned to the fasting level at 120 min. At 60 min, but not in the fasting state, the serum level of free fatty acids was inversely related to endothelium-dependent vasodilation (r=-0.74, P < 0.05), although no significant net changes in FFA levels were seen. Endothelium-independent vasodilation was not affected by the mixed meal. No similar attenuations in endothelium-dependent vasodilation were seen during control meals. In conclusion, an ordinary mixed meal transiently attenuated endothelium-dependent vasodilation. Free fatty acids may be involved in this effect on endothelial function.
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