- Moderate Postmeal Walking Has No Beneficial Effects Over Resting on Postprandial Lipemia, Glycemia, Insulinemia, and Selected Oxidative and Inflammatory Parameters in Older Adults with a Cardiovascular Disease Risk Phenotype: A Randomized Crossover Trial. [Journal Article]
- JNJ Nutr 2019 Jul 18
- CONCLUSIONS: In older adults with an increased CVD risk, the MD was associated with superior effects on several postprandial parameters (e.g., triglycerides), in comparison to the WD. Data revealed no relevant differences regarding the effects of postmeal walking and resting. None of the 4 treatments can be rated as superior regarding their acute effects on the shown postprandial metabolic, oxidative, and inflammatory parameters. The trial was registered at German Clinical Trials Register (DRKS; http://www.germanctr.de and http://www.drks.de) under identifier DRKS00012409.
- The Effect of Acute Continuous Hypoxia on Triglyceride Levels in Constantly Fed Healthy Men. [Journal Article]
- FPFront Physiol 2019; 10:752
- CONCLUSIONS: Acute hypoxia in healthy men tends to increase prandial VLDL-TG levels. These results lend support to the increased blood lipid levels reported in animals exposed acutely to lower partial pressures of oxygen.
- Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. [Journal Article]
- NMedNat Med 2019; 25(7):1096-1103
- Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1.…
Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus1. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension3-8. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.62 ± 7.02%, P = 0.002), and reduced insulinemia (-34.08 ± 7.12%, P = 0.006) and plasma total cholesterol (-8.68 ± 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 ± 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 ± 0.82 kg, P = 0.092) and hip circumference (-2.63 ± 1.14 cm, P = 0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.
- Short-Term Impact of Sucralose Consumption on the Metabolic Response and Gut Microbiome of Healthy Adults. [Journal Article]
- BJBr J Nutr 2019 Jul 01; :1-23
- Sucralose is an artificial non-nutritive sweetener used in foods aimed to reduce sugar and energy intake. While thought to be inert, the impact of sucralose on metabolic control has shown to be the o…
Sucralose is an artificial non-nutritive sweetener used in foods aimed to reduce sugar and energy intake. While thought to be inert, the impact of sucralose on metabolic control has shown to be the opposite. The gut microbiome has emerged as a factor shaping metabolic responses after sweetener consumption. We examined the short-term effect of sucralose consumption on glucose homeostasis and gut microbiome of healthy male volunteers. We performed a randomized, double-blind study in 34 subjects divided into two groups, one that was administered sucralose capsules (780 mg/day for seven days; n=17), and a control group receiving placebo (n=17). Before and after the intervention, glycemic and insulinemic responses were assessed with a standard oral glucose load (75 g). Insulin resistance was determined using HOMA-IR and Matsuda indexes. The gut microbiome was evaluated before and after the intervention by 16S rRNA sequencing. During the study, body weight remained constant in both groups. Glycemic control and insulin resistance were not affected during the 7-day period. At the phylum level, gut microbiome was not modified in any group. We classified subjects according to their change in insulinemia after the intervention, to compare the microbiome of responders and non-responders. Independent of consuming sucralose or placebo, individuals with a higher insulinemic response after the intervention had lower Bacteroidetes and higher Firmicutes abundances. In conclusion, consumption of high doses of sucralose for 7 days does not alter glycemic control, insulin resistance, or gut microbiome in healthy individuals. However, it highlights the need to address individual responses to sucralose.
- PDIA1/P4HB is required for efficient proinsulin maturation and β cell health in response to diet induced obesity. [Journal Article]
- EElife 2019 Jun 11; 8
- Regulated proinsulin biosynthesis, disulfide bond formation and ER redox homeostasis are essential to prevent Type two diabetes. In β cells, protein disulfide isomerase A1 (PDIA1/P4HB), the most abun…
Regulated proinsulin biosynthesis, disulfide bond formation and ER redox homeostasis are essential to prevent Type two diabetes. In β cells, protein disulfide isomerase A1 (PDIA1/P4HB), the most abundant ER oxidoreductase of over 17 members, can interact with proinsulin to influence disulfide maturation. Here we find Pdia1 is required for optimal insulin production under metabolic stress in vivo. β cell-specific Pdia1 deletion in young high-fat diet fed mice or aged mice exacerbated glucose intolerance with inadequate insulinemia and increased the proinsulin/insulin ratio in both serum and islets compared to wildtype mice. Ultrastructural abnormalities in Pdia1-null β cells include diminished insulin granule content, ER vesiculation and distention, mitochondrial swelling and nuclear condensation. Furthermore, Pdia1 deletion increased accumulation of disulfide-linked high molecular weight proinsulin complexes and islet vulnerability to oxidative stress. These findings demonstrate that PDIA1 contributes to oxidative maturation of proinsulin in the ER to support insulin production and β cell health.
- The deficiency and the supplementation of vitamin D and liver: Lessons of chronic fructose-rich diet in mice. [Journal Article]
- JSJ Steroid Biochem Mol Biol 2019 Jun 05; 192:105399
- The fructose added to soft drinks and processed food, as well as frequent detection of vitamin D deficiency in the body, are two insults increasingly considered to cause lesions in target organs. We …
The fructose added to soft drinks and processed food, as well as frequent detection of vitamin D deficiency in the body, are two insults increasingly considered to cause lesions in target organs. We studied the liver after a chronic high-fructose diet deficient and supplemented with vitamin D. Sixty C57BL/6 mature male mice were allocated into six groups (n = 10) for ten weeks: control (C), control deficient in vitamin D (CDD), control supplemented with vitamin D (CDS), fructose (F), fructose deficient in vitamin D (FDD), and fructose supplemented with vitamin D (FDS). The gene expressions of vitamin D receptor and CYP27B1 and 25 hydroxyvitamin D plasma level ensured that the diets caused vitamin D deficiency or supplementation. Body mass did not change, but blood pressure (BP) increased in CDD, F, and FDD, whereas BP was controlled in FDS. Insulinemia, insulin tolerance and resistance were seen in both vitamin D deficiency and fructose groups but improved with vitamin D supplementation. The steatosis and fibrosis were observed in the CDD, F and FDD groups. Also, F and FDD showed activation of stellate cells (HSC). Lipogenesis and inflammation gene expressions were enhanced in the CDD, F and FDD groups, but diminished with vitamin D supplementation. In conclusion, we demonstrated the adverse effects of vitamin D deficiency on metabolism, liver steatosis and, combined with fructose intake, liver interstitial fibrosis with hepatic stellate cell activation, and alteration of the lipogenesis, beta-oxidation, and liver inflammation. All these data improved when vitamin D was supplemented in the animals.
- The Bile Acid TUDCA Improves Beta-Cell Mass and Reduces Insulin Degradation in Mice With Early-Stage of Type-1 Diabetes. [Journal Article]
- FPFront Physiol 2019; 10:561
- Type 1 diabetes (T1D) is characterized by impairment in beta-cell mass and insulin levels, resulting in hyperglycemia and diabetic complications. Since diagnosis, appropriate control of glycaemia in …
Type 1 diabetes (T1D) is characterized by impairment in beta-cell mass and insulin levels, resulting in hyperglycemia and diabetic complications. Since diagnosis, appropriate control of glycaemia in T1D requires insulin administration, which can result in side effects, such as hypoglycemia. In this sense, some bile acids have emerged as new therapeutic targets to treat T1D and T2D, as well as metabolic diseases. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA) reduces the incidence of T1D development and improves glucose homeostasis in obese and T2D mice. However, its effects in early-stage of T1D have not been well explored. Therefore, we have assessed the effects of TUDCA on the glycemic control of mice with early-stage T1D. To achieve this, C57BL/6 mice received intraperitoneal administration of streptozotocin (STZ, 40 mg/kg) for 5 days. Once diabetes was confirmed in the STZ mice, they received TUDCA treatment (300 mg/kg) or phosphate buffered saline (PBS) for 24 days. After 15 days of treatment, the STZ+TUDCA mice showed a 43% reduction in blood glucose, compared with the STZ group. This reduction was likely due to an increase in insulinemia. This increase in insulinemia may be explained, at least in part, by a reduction in hepatic IDE activity and, consequently, reduction on insulin clearance, as well as an increase in beta-cell mass and a higher beta-cell number per islet. Also, the groups did not present any alterations in insulin sensitivity. All together, these effects contributed to the improvement of glucose metabolism in T1D mice, pointing TUDCA as a potential therapeutic agent for the glycemic control in early-stage of T1D.
- Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison to GCK-MODY (MODY2). [Journal Article]
- DDiabetes 2019 May 15
- Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsu…
Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemic-euglycemic clamps in three participant groups (n=10/group) with differing insulinemia and glycemia: healthy controls (euinsulinemia, euglycemia), glucokinase maturity-onset of the young (GCK-MODY; euinsulinemia, hyperglycemia), and type 1 diabetes (hyperinsulinemia, hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes. HbA1c was normal in controls and similarly elevated for type 1 diabetes and GCK-MODY. Basal insulin levels in control and GCK-MODY were nearly equal but were 2.5-fold higher in type 1 diabetes. Low-dose insulin infusion suppressed endogenous glucose production similarly in all groups and suppressed nonesterified fatty acids similarly between control and GCK-MODY, but to a lesser extent for type 1 diabetes. High-dose insulin infusion stimulated glucose disposal similarly in control and GCK-MODY, but was 29% and 22% less effective in type 1 diabetes, respectively. Multivariable linear regression showed insulinemia-but not glycemia-was significantly associated with muscle insulin sensitivity. These data suggest iatrogenic hyperinsulinemia predominates in driving insulin resistance in type 1 diabetes. Clinicaltrials.gov:NCT02971202.
- Preventive Effects of the Marine Microalga Phaeodactylum tricornutum, Used as a Food Supplement, on Risk Factors Associated with Metabolic Syndrome in Wistar Rats. [Journal Article]
- NNutrients 2019 May 14; 11(5)
- Long-chain polyunsaturated fatty acids, n-3 series (n-3 LC-PUFA), are known for their preventive effects against cardiovascular disease. In an unfavourable economic and environmental context of fish …
Long-chain polyunsaturated fatty acids, n-3 series (n-3 LC-PUFA), are known for their preventive effects against cardiovascular disease. In an unfavourable economic and environmental context of fish oil production, marine microalgae could be an alternative source of n-3 LC-PUFA and are of interest for human nutrition. The aim of this study was to evaluate the effects of P. tricornutum, a microalga rich in eicosapentaenoic acid and used as a food supplement, on the metabolic disorders associated with metabolic syndrome and obesity development. Three male Wistar rat groups (n = 6) were submitted for eight weeks to a standard diet or high-fat diet (HF) with 10% fructose in drinking water, supplemented or not with 12% of P. tricornutum (HF-Phaeo). Supplementation led to n-3 LC-PUFA enrichment of lipids in the liver, plasma and erythrocytes. Plasma transaminases showed no difference between the HF and HF-Phaeo groups. Body weight, fat mass, inflammatory markers and insulinemia decreased in HF-Phaeo rats versus the HF group. Plasma total cholesterol, triacylglycerols and leptine diminished in HF-Phaeo rats, while HDL-cholesterol increased. In conclusion, this study highlights the beneficial effects of P. tricornutum in reducing the metabolic disorders associated with metabolic syndrome.
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- Sitagliptin's effects on bone tissue and osseointegration in diabetic rats. [Journal Article]
- AOArch Oral Biol 2019; 102:238-243
- CONCLUSIONS: In this model, sitagliptin administration did not reverse the negative effects of type I diabetes on bone, suggesting that sitagliptin has no direct action on bone tissue and has no protective bone action in decompensated diabetic animals.