Mumefural prevents insulin resistance and amyloid-beta accumulation in the brain by improving lowered interstitial fluid pH in type 2 diabetes mellitus

Abstract

The present study tried to clarify if mumefural would prevent hyperglycemia, one of the typical symptoms of type 2 diabetes mellitus (T2DM), since mumefural is an extract from Japanese apricots preventing hyperglycemia. To clarify if mumefural would prevent T2DM pathogenesis, we used Otsuka Long-Evans Tokushima fatty (OLETF) rats, T2DM model. Mumefural diminished hyperglycemia, HOMA-IR and plasma triglyceride concentration in OLETF rats under fasting conditions. In addition, mumefural elevated protein expression of sodium-coupled monocarboxylate transporter 1 (SMCT1) in the distal colon participating in absorption of weak organic acids, which behave as bases but not acids after absorption into the body. Mumefural also increased the interstitial fluid pH around the brain hippocampus lowered in OLETF rats compared with non-T2DM LETO rats used as control for OLETF rats. Amyloid-beta accumulation in the brain decreased in accordance with the pH elevation. On the one hand, mumefural didn't affect plasma concentrations of glucagon, GLP-1, GIP or PYY under fasting conditions. Taken together, these observations indicate that: 1) mumefural would be a useful functional food improving hyperglycemia, insulin resistance and the lowered interstitial fluid pH in T2DM; 2) the interstitial fluid pH would be one of key factors influencing the accumulation of amyloid-beta.

Physiological roles of chloride ions in bodily and cellular functions

“…pH is lowered by H + and CO 2 produced in metabolic cells such as myocytes, neurons, etc., H + is produced via glycolysis, and also from CO 2 (CO 2 ↔ H + + HCO 3 − ) via TCA cycle in mitochondria: the produced H + plays various important roles in cellular functions [ 201 , 217 – 237 ]. Lowered pH disturbs various body functions such as appearance of insulin resistance, enhancement of cancer metastasis and elevation of amyloid-ß production [ 201 , 217 – 235 ]. In peripheral tissues, CO 2 produced by metabolic cells moves to capillary erythrocytes, where CO 2 is converted to H + and HCO 3 − via a carbonic anhydrase (CA)-facilitated process.…”

The Role of Ion-Transporting Proteins in Human Disease

“…Thus, the acidic conditions which occur in type 2 diabetes patients increases the production of amyloid-β by activating the β-and γ-secretases [68][69][70]77]. Therefore, the interstitial fluid's pH should be maintained within the normal range by various ion transporting proteins and elevating the pH-buffer capacity to ensure the maintenance of healthy body conditions [48,85,86] (Figure 5). Thus, ion-transporting proteins' dysfunction play important roles in human diseases.…”