Abstract
The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1), require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.
Highlights
Type 2 diabetes (T2D) is one of the most prevalent human metabolic diseases and has rapidly emerged as a global health care problem reaching epidemic proportions in recent years [1]
Among several tripeptides that affected glucose levels, we identified one, referred as Diapin that was more effective than the others in lowering blood glucose level in C57BL/6J mice after oral loading of glucose
We have not examined all possible combinations of tripeptides, our finding suggests that Diapin, but not all tripeptides, can effectively lower blood glucose in mice
Summary
Type 2 diabetes (T2D) is one of the most prevalent human metabolic diseases and has rapidly emerged as a global health care problem reaching epidemic proportions in recent years [1]. T2D is characterized by hyperglycemia resulting from insulin resistance and relative deficiency of insulin due to the reduction of functional b-cell mass [2]. Current therapies for T2D include increasing plasma insulin levels, improving insulin sensitivity of tissues, and reducing carbohydrate absorption from the gastrointestinal tract [3]. Insulin, produced by b-cells of the pancreas, is a key hormone in regulating of carbohydrate and fat metabolism in the body. Either by direct insulin administration or by agents that promote insulin secretion and preserve functional bcell mass, is a key goal in the treatment of T2D. Glucagon-like peptide-1 (GLP-1), mainly produced by the intestinal L-cell, stimulates glucose-dependent insulin secretion and protects b-cells [4,5,6]. The therapeutic insulin and GLP-1, require injections, which are costly and inconvenient, resulting in less patient compliance
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