Monounsaturated Fatty Acid Diets Improve Glycemic Tolerance through Increased Secretion of Glucagon-Like Peptide-1*

Abstract

Diets enriched in monounsaturated fatty acids (MUFA)s have been shown to benefit glycemic control. Furthermore, MUFAs specifically stimulate secretion of the antidiabetic hormone, Glucagon-like peptide-1 (GLP-1) in vitro. To determine whether the MUFA-induced benefit in glycemic tolerance in vivo is due to increased GLP-1 release, lean Zucker rats were pair-fed a synthetic diet containing 5% fat derived from either olive oil (OO; 74% MUFA) or coconut oil (CO; 87% saturated fatty acids; SFA) for 2 weeks. Food intake and body weight gain were similar for both groups over the feeding period. The OO group had improved glycemic tolerance compared with the CO group in both oral and duodenal glucose tolerance tests [area under curve (AUC) 121 +/- 61 vs. 290 +/- 24 mM.120 min, P < 0.05; and 112 +/- 28 vs. 266 +/- 65 mM.120 min, P < 0.05, respectively]. This was accompanied by increased secretion of gut glucagon-like immunoreactivity (gGLI; an index of GLP-1 levels) in the OO rats compared with the CO rats (402 +/- 96 vs. 229 +/- 33 pg/ml at t = 10 min, P < 0.05). Tissue levels of GLP-1 and plasma insulin and glucagon levels were not different between the two groups. To determine the total contribution of GLP-1 to the enhanced glycemic tolerance in OO rats, the GLP-1 receptor antagonist exendin(9-39) (Ex(9-39)) was infused 3 min before a duodenal glucose tolerance test. Ex(9-39) abolished the benefit in glycemic tolerance conferred by OO feeding (OO+Ex(9-39) vs. CO+Ex(9-39), P = NS), and resulted in a deterioration of glycemic tolerance in the OO+Ex(9-39) group when compared with the OO controls (AUC 331 +/- 21 vs. 112 +/- 28 mM.120 min, P < 0.05). To probe the mechanism by which the OO diet enhanced GLP-1 secretion, a GLP-1-secreting L cell line was incubated for 24 h with either 100 microM oleic acid (MUFA) or 100 microM palmitic acid (SFA) and subsequently challenged with GIP, a known stimulator of the L cell. Preexposure to oleic acid but not to palmitic acid significantly increased GIP-induced GLP-1 secretion when compared with controls (55 +/- 12% vs. 34 +/- 9%, P < 0.01). These results demonstrate that the benefit in glycemic tolerance obtained with MUFA diets occurs in association with increased GLP-1 secretion, through a mechanism of enhanced L cell sensitivity. These results suggest that diet therapy with MUFAs may be useful for the treatment of patients with impaired glucose tolerance and/or type 2 diabetes through increased GLP-1 secretion.

Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo

“…GIP and GLP-1 are released from the gut in response to nutrient intake and in turn stimulate insulin secretion from pancreatic ␤-cells (1,2,6,10,14,15,23,28,29,31,32,34,45,48,49,51). Increasing the release of these incretin hormones by oral agents may be an attractive approach to improve glucose homeostasis in subjects with diabetes mellitus.…”

“…Both hormones are known as "incretin" hormones, as they are released from the gut in response to dietary nutrients (1,2,6,10,14,15,23,28,29,34,45,48,49,51) and stimulate synthesis and release of insulin from pancreatic ␤-cells, while also promoting ␤-cell growth and survival (4,58). In view of these actions, there is significant interest in harnessing incretins to treat diabetes.…”

Intraduodenal milk protein concentrate augments the glycemic and food intake suppressive effects of DPP-IV inhibition

“…While all three macronutrient classes elicit GLP-1 secretion (16,23,27,36,40,43,55), it remains to be determined whether there are differences in the behavioral and physiological effects produced by GLP-1 signaling following intraintestinal exposure to an isolated macronutrient from one food group compared with another (i.e., protein derived from dairy versus soy). Thus one hypothesis regarding the relationship between regular dairy consumption and reduced body weight gain (11,60) is that the unique macronutrient constituents found within dairy foods may enhance gastrointestinal (GI)-derived satiation signaling through increased secretions of specific gut peptides like GLP-1.…”

Glycemic Index of Indian Cereal Staple Foods and their Relationship to Diabetes and Metabolic Syndrome

“…As a result, butter is more absorbed into the portal vein rather than transported for chylomicron synthesis, and this further increases the hepatic glucose output and thereby results in a high plasma glucose level. 117 Diets rich in MUFA help in stimulating GLP secretion by enhancing L cell sensitivity, 118 and these incretin hormones (including GIP) are being used as a new therapeutic approach in the treatment of type 2 diabetes. 119 …”