Suppression of Postprandial Blood Glucose Fluctuations by a Low-Carbohydrate, High-Protein, and High-Omega-3 Diet via Inhibition of Gluconeogenesis

Abstract

Hyperglycemia significantly contributes to the development and progression of metabolic diseases. Managing postprandial blood glucose fluctuations is of particular importance for patients with hyperglycemia, but safe and effective means of reducing blood glucose levels are still lacking. Five diets with varying macronutrient ratios and omega-3 fatty acid amounts were tested for their blood glucose-lowering effects in male C57BL/6J mice. The diets with potent blood glucose-lowering effects were further investigated for their underlying mechanisms and their beneficial effects on hyperglycemia models. Mice given the low-carbohydrate, high-protein, and high-omega-3 (LCHP+3) diet exhibited a rapid reduction of the blood glucose levels that remained consistently low, regardless of feeding. These effects were associated with reduced amino acid gluconeogenesis, due to the inhibition of hepatic alanine transaminase (ALT). Furthermore, the LCHP+3 intervention was effective in reducing the blood glucose levels in several disease conditions, including type 1 diabetes mellitus, hormone-induced hyperglycemia, and diet-induced metabolic syndrome. Our findings identify the LCHP+3 diet as a potent blood glucose-lowering diet that suppresses postprandial blood glucose fluctuations through the inhibition of gluconeogenesis and may have great clinical utility for the management of metabolic diseases with hyperglycemia.

Lkb1 suppresses amino acid-driven gluconeogenesis in the liver

“…The fasting hyperglycemia phenotype of the mutant mice was partially rescued by treatment with a pan inhibitor of aminotransferases, AOA, consistent with the critical role of aminotransferases, which are frequently involved in the first step of amino acid catabolism. Consistent with our data, a recent study showed that inhibition of the hepatic alanine transaminase reduced amino acid gluconeogenesis and was associated with a reduced postprandial blood glucose and the rescue of the hyperglycemia phenotype of different models of diabetes 42 . In addition our data highlight a role for Agxt a serine-pyruvate transaminase involved in both gluconeogenesis from serine 22 and glyoxylate detoxification.…”

CompromisedDNArepair is responsible for diabetes‐associated fibrosis

“…Thus, to simulate the pathological consequences of high blood sugar spikes in cultured cells in short time, we used high sugar concentrations. Moreover, considering the clinical scores of poorly managed diabetes in juvenile or a postprandial slot, the glucose levels in diabetics can be around 12-20 mM and the levels of other reducing sugars such as fructose or ribose can be around (0.6-1.9 mM) or (~100 lM), respectively (Gross & Zollner, 1991;Sidhu et al, 2001;Clark et al, 2014;Laughlin, 2014;Chen et al, 2017;Wang et al, 2018). Thus, to simulate the pathologically relevant hyperglycemic conditions, the DNA repair studies were repeated with cells maintained under 17 mM glucose (for 5, 10, or 15 days).…”

Vitamin D and ω-3 Supplementations in Mediterranean Diet During the 1st Year of Overt Type 1 Diabetes: A Cohort Study

“…This finding, if confirmed by further RCTs, might be considered for assisting children beginning at the onset of the disease. The clinical outcome of a reduced insulin demand, mainly at meals, is compatible with the hypothesis of the inhibition of postprandial protein neoglucogenesis [10]. Interestingly, the effects of co-supplementation of vitamin D and ω-3 have also been reported in randomized clinical trials outside of childhood T1D, on gestational diabetes and on multiple sclerosis [32,33].…”

“…The ability of ω-3 to counteract the pathogenic pathways of T1D has been highlighted in two studies showing that its nutritional intake may reduce blood glucose levels [10] and limit β-cells apoptosis mediated by glucolipotoxicity [11]. Specifically, diet supplementation with ω-3 was found to lead to reduction of postprandial glycemia and improvement of glycemic variability, mediated by the inhibition of neoglucogenesis [10], and counteracting β-cell apoptosis through activation of the Eovl2 /docosahexaenoic acid(DHA) enzyme axis [11]. These reports suggest both an immunologic and metabolic role for ω-3, limiting the post-prandial blood glucose increase, and protecting β-cell apoptosis induced by glucolipotoxicity.…”