casein-hydrolysate and Hyperglycemia

Ingestion of high doses of casein hydrolysate stimulates insulin secretion in healthy subjects and patients with type 2 diabetes. The effects of low doses have not been studied. The aim of this study was to assess the effect of lower doses of a casein hydrolysate on the glucose and insulin responses to an oral glucose tolerance test in patients with type 2 diabetes.. In this randomized, placebo-controlled, double-blind study, thirteen patients with type 2 diabetes (age: 58±1 years) were studied. Glucose, insulin and C-peptide responses were determined after the oral administration of 0 (control), 6 or 12 g protein hydrolysate in combination with 50 g carbohydrate.. Twelve grams of casein hydrolysate, but not 6g, elevated insulin levels and decreased glucose levels post-challenge. These changes over time were not large enough to also affect the total area under the curve of glucose and insulin. C-peptide levels did not change after both treatments.. Ingestion of six grams of casein hydrolysate did not affect glucose or insulin responses. Intake of 12 g of casein hydrolysate has a small positive effect on post-challenge insulin and glucose levels in patients with type 2 diabetes.

Topics: Blood Glucose; C-Peptide; Caseins; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Treatment Outcome

High protein feeding improves glucose homeostasis in rodents and humans with diabetes, but the mechanisms that underlie this improvement remain elusive. Here we show that acute administration of casein hydrolysate directly into the upper small intestine increases glucose tolerance and inhibits glucose production in rats, independently of changes in plasma amino acids, insulin levels, and food intake. Inhibition of upper small intestinal peptide transporter 1 (PepT1), the primary oligopeptide transporter in the small intestine, reverses the preabsorptive ability of upper small intestinal casein infusion to increase glucose tolerance and suppress glucose production. The glucoregulatory role of PepT1 in the upper small intestine of healthy rats is further demonstrated by glucose homeostasis disruption following high protein feeding when PepT1 is inhibited. PepT1-mediated protein-sensing mechanisms also improve glucose homeostasis in models of early-onset insulin resistance and obesity. We demonstrate that preabsorptive upper small intestinal protein-sensing mechanisms mediated by PepT1 have beneficial effects on whole-body glucose homeostasis.

Topics: Amino Acids; Animals; Caseins; Diabetes Mellitus, Type 2; Diet, High-Protein; Glucose; Hyperglycemia; Insulin; Intestinal Absorption; Intestine, Small; Male; Peptide Transporter 1; Protein Transport; Rats; Rats, Sprague-Dawley

Activation of the nod-like receptor protein 3 (NLRP3) inflammasome is required for IL-1β release and is a key component of obesity-induced inflammation and insulin resistance. This study hypothesized that supplementation with a casein hydrolysate (CH) would attenuate NLRP3 inflammasome mediated IL-1β secretion in adipose tissue (AT) and improve obesity-induced insulin resistance.. J774.2 macrophages were LPS primed (10 ng/mL) and stimulated with adenosine triphosphate (5 mM) to assess NLRP3 inflammasome activity. Pretreatment with CH (1 mg/mL; 48 h) reduced caspase-1 activity and decreased IL-1β secretion from J774.2 macrophages in vitro. 3T3-L1 adipocytes cultured with conditioned media from CH-pretreated J774.2 macrophages demonstrated increased phosphorylated (p)AKT expression and improved insulin sensitivity. C57BL/6JOLaHsd mice were fed chow or high fat diet (HFD) for 12 wk ± CH resuspended in water (0.5% w/v). CH supplementation improved glucose tolerance in HFD-fed mice as determined by glucose tolerance test. CH supplementation increased insulin-stimulated pAKT protein levels in AT, liver, and muscle after HFD. Cytokine secretion was measured from AT and isolated bone marrow macrophages cultured ex vivo. CH supplementation attenuated IL-1β, tumor necrosis factor alpha (TNF-α) and IL-6 secretion from AT and IL-1β, IL-18, and TNF-α from bone marrow macrophages following adenosine triphosphate stimulation ex vivo.. This novel CH partially protects mice against obesity-induced hyperglycemia coincident with attenuated IL-1β secretion and improved insulin signaling.

Topics: 3T3-L1 Cells; Adipose Tissue; Animals; Caseins; Cytokines; Diabetes Mellitus, Type 2; Diet, High-Fat; Hyperglycemia; Inflammasomes; Inflammation; Insulin; Insulin Resistance; Interleukin-1beta; Interleukin-6; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; Obesity; Tumor Necrosis Factor-alpha