Percutaneous closure of the patent foramen ovale

A patent foramen ovale (PFO) is a common finding present in 25% of the population. A relationship between PFO and several clinical conditions such as stroke, migraine, platypnea-orthodeoxia syndrome, neurological decompression illness in divers, high altitude pulmonary edema, sleep apnea, and economy class syndrome have been documented. Observational non-randomized studies have shown percutaneous PFO closure more effective than medical treatment for stroke prevention, in particular in patients with complete closure as well as in patients with more than one cerebrovascular event at baseline. In the case of migraine, PFO closure has been shown to result in a marked reduction in migraine burden or migraine days. PFO anatomy, epidemiological data on associated clinical conditions, comparison between percutaneous closure and medical treatment, as well as the technical aspect of the procedure are described in this review

Effects of glucagon in the control of endogenous glucose production in man

Endogenous glucose production has been shown to increase during administration of glucagon + fructose, but not during administration of fructose alone. To determine the mechanisms by which glucagon exerts this action, endogenous glucose production (EGP) and gluconeogenesis from fructose (GNF) were measured in eight healthy subjects infused 1) with graded doses of glucagon (2 and 4 ng.kg-1.min-1 for 3 h each) during constant infusion of 13C-fructose (3 mg.kg-1.min-1), and 2) with graded doses of 13C-fructose (3 and 6 mg.kg-1.min-1) during constant glucagon infusion (2 ng.kg-1.min-1). GNF was estimated from 13C-glucose synthesis. In both protocols, infusion of 3 mg.kg-1.min-1 fructose + 2 ng.kg-1.min-1 glucagon increased EGP by 5-8% (P < 0.05), while GNF represented 43-49% of EGP. Thereafter, increasing the glucagon infusion rate further increased EGP to 118 +/- 3% of basal values (P < 0.01) without altering the proportion due to GNF. In contrast, increasing the fructose infusion rate at constant glucagonemia increased EGP similarly (by 19 +/- 4%, P < 0.05) but enhanced the contribution of GNF to 76 +/- 2% (P < 0.001). Graded infusion of glucagon or fructose alone failed to stimulate EGP. The present findings indicate that hyperglucagonemia stimulates endogenous glucose production during fructose infusion. This effect is not secondary to a stimulation of gluconeogenesis, but to a channelling of glucose-6-phosphate towards systemic release

Non oxidative fructose disposal is not inhibited by lipids in humans.

peer reviewedElevated free fatty acid concentrations are known to decrease insulin-mediated glucose uptake, glucose oxidation and glycogen synthesis. In order to determine whether free fatty acids inhibit glycogen synthesis at the level of liver cells, the effects of an infusion of lipids on carbohydrate metabolism were investigated in healthy subjects during a two-step (16.7 and 33.4 mumol/(kg.min) 13C-fructose infusion. Fructose infusion dose-dependently stimulated fructose (measured from 13CO2 production) and net carbohydrate oxidation (measured with indirect calorimetry). It also stimulated systemic 13C glucose appearance, indicating a dose-dependent stimulation of gluconeogenesis. Net glucose output (measured with 6,6 2H glucose) was however not altered. Lipid infusion significantly reduced fructose oxidation (measured from 13CO2 production) at both rates of fructose infusion, but did not alter plasma fructose or lactate concentrations, nor plasma 13C glucose appearance or net glucose production. Non oxidative fructose disposal was increased by 31% (p < 0.05) at the lowest, and by 18% (p < 0.01) at the highest infusion rate. Since nonoxidative fructose disposal corresponds mainly to liver glycogen deposition, these results suggest that lipid infusion increased hepatic glycogen synthesis, and hence that hepatic glycogen synthase is not inhibited by fatty acids

Non oxidative fructose disposal is not inhibited by lipids in humans

Elevated free fatty acid concentrations are known to decrease insulin-mediated glucose uptake, glucose oxidation and glycogen synthesis. In order to determine whether free fatty acids inhibit glycogen synthesis at the level of liver cells, the effects of an infusion of lipids on carbohydrate metabolism were investigated in healthy subjects during a two-step (16.7 and 33.4 mumol/(kg.min) 13C-fructose infusion. Fructose infusion dose-dependently stimulated fructose (measured from 13CO2 production) and net carbohydrate oxidation (measured with indirect calorimetry). It also stimulated systemic 13C glucose appearance, indicating a dose-dependent stimulation of gluconeogenesis. Net glucose output (measured with 6,6 2H glucose) was however not altered. Lipid infusion significantly reduced fructose oxidation (measured from 13CO2 production) at both rates of fructose infusion, but did not alter plasma fructose or lactate concentrations, nor plasma 13C glucose appearance or net glucose production. Non oxidative fructose disposal was increased by 31% (p &lt; 0.05) at the lowest, and by 18% (p &lt; 0.01) at the highest infusion rate. Since nonoxidative fructose disposal corresponds mainly to liver glycogen deposition, these results suggest that lipid infusion increased hepatic glycogen synthesis, and hence that hepatic glycogen synthase is not inhibited by fatty acids

Effect of chronic intracerebroventricular infusion of insulin on brown adipose tissue activity in fed and fasted rats

OBJECTIVES: Carbohydrate feeding stimulates, and fasting decreases the sympathetic nervous system activity and brown adipose tissue (BAT) thermogenesis. This study was performed to assess the hypothesis that these effects were secondary to changes in insulin concentrations in the central nervous system. METHODS: BAT sympathetic activity was assessed by comparing 3H-GDP binding to isolated mitochondria of innervated and denervated interscapular BAT of three groups of 10 week old male Wistar rats: food-restricted, 48 h fasted or ad libitum fed. During the three days preceding this measurement, animals received a continuous intracerebroventricular (ivc) infusion of insulin (0.48 U/d) or vehicle. RESULTS: In food-restricted rats, 3H-GDP binding to mitochondria of innervated BAT was 41% higher than that to denervated BAT. Icv insulin did not stimulate 3H-GDP binding in innervated BAT.In 48 h fasted rats, 3H-GDP binding to mitochondria of innervated BAT was reduced by 30-50%, while the activity of denervated BAT was minimally affected. Icv insulin did not prevent this fasting-induced drop in BAT. In rats fed ad libitum, icv insulin decreased food intake by 17% (P &lt; 0.05) and increased 3H-GDP binding to innervated BAT by 27% (P &lt; 0.05). CONCLUSION: Intracerebroventricular insulin stimulates BAT activity in rats fed ad libitum but not in food-restricted or fasted rats. This demonstrates that the decrease in BAT activity observed during fasting is unlikely to be due to a decrease in insulin concentration in the nervous system

Glucose utilization and production in patients with maturity-onset diabetes of the young caused by a mutation of the hepatocyte nuclear factor-1alpha gene

Mutations of the hepatocyte nuclear factor (HNF)-1alpha gene cause impaired insulin secretion and hyperglycemia in patients with maturity-onset diabetes of the young (MODY)3. Whether these mutations also affect glucose metabolism in tissues other than the beta-cell has not yet been documented. We therefore assessed, in five MODY3 patients and a dozen healthy control subjects, insulin secretion, oxidative and nonoxidative glucose disposal, and glucose production during a two-step hyperglycemic clamp and a euglycemic hyperinsulinemic (0.4 mU x kg(-1) x min(-1)) clamp. Compared with healthy control subjects, MODY3 patients had higher fasting plasma glucose (+100%) but similar rates of fasting glucose production and oxidation. Both the early and late phases of insulin secretion were virtually abolished during the hyperglycemic clamp, and glucose production was suppressed by only 43% in MODY3 patients vs. 100% in healthy control subjects. The rate of glucose infusion required to produce a 5 mmol/l increase above basal glycemia was reduced by 30%, net nonoxidative glucose disposal (which is equal to net glycogen deposition) was inhibited by 39%, and net carbohydrate oxidation during hyperglycemia was 25% lower in MODY3 patients compared with control subjects. Insulin-stimulated glucose utilization and oxidation measured during the hyperinsulinemic clamp (at approximately 200 pmol/l insulin) were identical in MODY3 patients and in healthy control subjects, indicating that peripheral insulin sensitivity was not altered. Suppression of endogenous glucose production was, however, mildly impaired. It is concluded that MODY3 patients have severely depressed glucose-induced insulin secretion. The development of hyperglycemia in these patients appears to be caused by a decreased stimulation of glucose utilization, oxidation, and nonoxidative glucose disposal as well as by a blunted suppression of endogenous glucose output. These phenomena are essentially secondary to insulinopenia, whereas insulin sensitivity remains intact