Branched-chain amino acids supplementation protects streptozotocin-induced insulin secretion and the correlated mechanism

Background: Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described.Objective: To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance.Design: Ninety-five non-diabetic Chinese subjects (43 females) underwent a mixed-meal tolerance test; blood biomarkers including BCAAs (leucine, isoleucine, valine) were measured for 6 h. Fasting and postprandial insulin secretion rates (ISR) and insulin clearance were determined by oral minimal modeling of glucose and C-peptide.Results: Fasting and postprandial plasma BCAA correlated strongly with each other (ρ = 0.796, P < 0.001), and both were positively associated with basal ISR (ρ = 0.45/0.36, P < 0.001), total postprandial ISR AUC (ρ = 0.37/0.45, P < 0.001), and negatively with insulin clearance (ρ = −0.29/−0.29, P < 0.01), after adjusting for sex and body mass index. These relationships largely persisted after adjusting further for insulin resistance and postprandial glucose. Compared with subjects in the middle and lowest tertiles for fasting or postprandial plasma BCAA, subjects in the highest tertile had significantly greater postprandial glucose (by 7–10%) and insulin (by 74–98%) concentrations, basal ISRs (by 34–53%), postprandial ISR AUCs (by 41–49%), and lower insulin clearance rates (by 17–22%) (all P < 0.05).Conclusions: Fasting and postprandial plasma BCAA levels are associated with greater fasting and postprandial insulin secretion and reduced insulin clearance in healthy Chinese subjects. These observations potentially highlight an additional layer of involvement of BCAA in the regulation of glucose homeostasis.

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769-P: Short-Term Dietary Reduction of Branched-Chain Amino Acids Reduces Meal-Induced Insulin Secretion and Modifies Microbiome Composition in Overweight Patients with Type 2 Diabetes

Diabetes ◽

10.2337/db19-769-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 769-P

Author(s):

YANISLAVA KARUSHEVA ◽

THERESA VAN GEMERT ◽

KLAUS STRASSBURGER ◽

DANIEL F. MARKGRAF ◽

TOMAS JELENIK ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Insulin Secretion ◽

Branched Chain Amino Acids ◽

Short Term ◽

Microbiome Composition ◽

Branched Chain

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Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz191 ◽

2019 ◽

Vol 110 (5) ◽

pp. 1098-1107 ◽

Cited By ~ 15

Author(s):

Yanislava Karusheva ◽

Theresa Koessler ◽

Klaus Strassburger ◽

Daniel Markgraf ◽

Lucia Mastrototaro ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Adipose Tissue ◽

Insulin Secretion ◽

Crossover Trial ◽

Branched Chain Amino Acids ◽

Short Term ◽

Microbiome Composition ◽

Branched Chain

ABSTRACT Background Epidemiological studies have shown that increased circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and type 2 diabetes (T2D). This may result from altered energy metabolism or dietary habits. Objective We hypothesized that a lower intake of BCAAs improves tissue-specific insulin sensitivity. Methods This randomized, placebo-controlled, double-blinded, crossover trial examined well-controlled T2D patients receiving isocaloric diets (protein: 1 g/kg body weight) for 4 wk. Protein requirements were covered by commercially available food supplemented ≤60% by an AA mixture either containing all AAs or lacking BCAAs. The dietary intervention ensured sufficient BCAA supply above the recommended minimum daily intake. The patients underwent the mixed meal tolerance test (MMT), hyperinsulinemic-euglycemic clamps (HECs), and skeletal muscle and white adipose tissue biopsies to assess insulin signaling. Results After the BCAA− diet, BCAAs were reduced by 17% during fasting (P < 0.001), by 13% during HEC (P < 0.01), and by 62% during the MMT (P < 0.001). Under clamp conditions, whole-body and hepatic insulin sensitivity did not differ between diets. After the BCAA− diet, however, the oral glucose sensitivity index was 24% (P < 0.01) and circulating fibroblast-growth factor 21 was 21% higher (P < 0.05), whereas meal-derived insulin secretion was 28% lower (P < 0.05). Adipose tissue expression of the mechanistic target of rapamycin was 13% lower, whereas the mitochondrial respiratory control ratio was 1.7-fold higher (both P < 0.05). The fecal microbiome was enriched in Bacteroidetes but depleted of Firmicutes. Conclusions Short-term dietary reduction of BCAAs decreases postprandial insulin secretion and improves white adipose tissue metabolism and gut microbiome composition. Longer-term studies will be needed to evaluate the safety and metabolic efficacy in diabetes patients. This trial was registered at clinicaltrials.gov as NCT03261362.

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Effect of Reduced Intake of Branched-Chain Amino Acids (BCAA) on Insulin Secretion and Sensitivity in Type 2 Diabetes

Diabetes ◽

10.2337/db18-773-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 773-P

Author(s):

YANISLAVA KARUSHEVA ◽

THERESA VAN GEMERT ◽

MARIE-CHRISTINE SIMON ◽

DANIEL F. MARKGRAF ◽

KLAUS STRASSBURGER ◽

...

Keyword(s):

Type 2 Diabetes ◽

Amino Acids ◽

Insulin Secretion ◽

Branched Chain Amino Acids ◽

Branched Chain

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Only L-valine among branched-chain amino acids is effective in promoting the growth of the small intestinal mucosa

Gastroenterology ◽

10.1016/s0016-5085(01)83364-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A676-A676

Author(s):

T TAKAHASHI ◽

H DOI ◽

H KOMATSU ◽

K SATO ◽

O UEDA ◽

...

Keyword(s):

Amino Acids ◽

Intestinal Mucosa ◽

Branched Chain Amino Acids ◽

Small Intestinal Mucosa ◽

Small Intestinal ◽

Branched Chain

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The Weight Loss Effects of Branched Chain Amino Acids and Vitamin B6: A Randomized Controlled Trial on Obese and Overweight Women

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000511 ◽

2018 ◽

Vol 88 (1-2) ◽

pp. 80-89 ◽

Cited By ~ 3

Author(s):

Zahra Shakibay Novin ◽

Saeed Ghavamzadeh ◽

Alireza Mehdizadeh

Keyword(s):

Amino Acids ◽

Weight Loss ◽

Body Composition ◽

Vitamin B6 ◽

Controlled Trial ◽

Density Lipoprotein ◽

Branched Chain Amino Acids ◽

Model Assessment ◽

Waist To Hip Ratio ◽

Branched Chain

Abstract. Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25–34.9 kg/m2). Taking a four-week moderate deficit calorie diet (–500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (–2.43 ± 1.02 kg) or placebo (–1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.

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