Structural Aspects of Gut Peptides with Therapeutic Potential for Type 2 Diabetes

ChemMedChem ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. 560-567 ◽  
Author(s):  
Chandralal M. Hewage ◽  
Kalyana C. Venneti
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Potential ◽  
Gut Peptides ◽  
Structural Aspects

Proglucagon-Derived Peptides: Mechanisms of Action and Therapeutic Potential

Physiology ◽  
2005 ◽  
Vol 20 (5) ◽  
pp. 357-365 ◽  
Author(s):  
Elaine M Sinclair ◽  
Daniel J. Drucker
Keyword(s):  
Type 2 Diabetes ◽  
Human Disease ◽  
Clinical Relevance ◽  
Therapeutic Potential ◽  
Mechanisms Of Action ◽  
Receptor Antagonists ◽  
Glucagon Receptor ◽  
Receptor Agonists ◽  
Glucagon Like Peptide

Glucagon is used for the treatment of hypoglycemia, and glucagon receptor antagonists are under development for the treatment of type 2 diabetes. Moreover, glucagon-like peptide (GLP)-1 and GLP-2 receptor agonists appear to be promising therapies for the treatment of type 2 diabetes and intestinal disorders, respectively. This review discusses the physiological, pharmacological, and therapeutic actions of the proglucagon-derived peptides, with an emphasis on clinical relevance of the peptides for the treatment of human disease.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

scholarly journals Biological activity and mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulphated derivatives

2016 ◽  
Vol 62 (1) ◽  
pp. 22-30 ◽  
Author(s):  
A.M. Popov ◽  
O.N. Krivoshapko ◽  
A.A. Klimovich ◽  
A.A. Artyukov
Keyword(s):  
Type 2 Diabetes ◽  
Biological Activity ◽  
Lipid Metabolism ◽  
Phenolic Compounds ◽  
Rosmarinic Acid ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Therapeutic Action ◽  
Carbohydrate And Lipid Metabolism

The review considers recent experimental studies of biological activity and mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulfated derivatives in diseases associated with disorders of carbohydrate and lipid metabolism. Particular attention is focused on the results of studies showing a high therapeutic potential of these phenolic compounds in their prophylactic and therapeutic use at experimental modeling of type 2 diabetes and hyperlipidemia. Based on the analysis of our results and the literature data putative mechanisms of therapeutic action of rosmarinic acid, luteolin and its sulfated derivatives have been proposed.

scholarly journals Role of Gut-Related Peptides and Other Hormones in the Amelioration of Type 2 Diabetes after Roux-en-Y Gastric Bypass Surgery

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Mirella P. Hage ◽  
Bassem Safadi ◽  
Ibrahim Salti ◽  
Mona Nasrallah
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Cell Function ◽  
Gastric Bypass Surgery ◽  
Gastrointestinal Hormones ◽  
Gut Peptides

Bariatric surgery is currently the most effective and durable therapy for obesity. Roux-en-Y gastric bypass surgery, the most commonly performed procedure worldwide, causes substantial weight loss and improvement in several comorbidities associated with obesity, especially type 2 diabetes. Several mechanisms are proposed to explain the improvement in glucose metabolism after RYGB surgery: the caloric restriction and weight loss per se, the improvement in insulin resistance and beta cell function, and finally the alterations in the various gastrointestinal hormones and adipokines that have been shown to play an important role in glucose homeostasis. However, the timing, exact changes of these hormones, and the relative importance of these changes in the metabolic improvement postbariatric surgery remain to be further clarified. This paper reviews the various changes post-RYGB in adipokines and gut peptides in subjects with T2D.

scholarly journals Type2Diabetes—Effect of Compensatory Oversecretion as a Reason forβ-Cell Collapse

2002 ◽  
Vol 3 (3) ◽  
pp. 153-158 ◽  
Author(s):  
Valdemar Grill ◽  
Anneli Björklund
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Clinical Studies ◽  
Structural Damage ◽  
Therapeutic Potential ◽  
Cell Collapse

Insulin secretion declines progressively before and during the course of type 2 diabetes. Evidence indicates that this process is, in part, secondary to increased requirement for insulin secretion that is brought about by insulin resistance and by hyperglycemia. The effects of over-secretion extend far beyond a mere reduction of available insulin stores and may cause not only functional but also structural damage. The time is ripe for clinical studies, which explore the therapeutic potential of reducing over-secretion.

Targeting the circadian system

2018 ◽  
Author(s):  
Gregory D. M. Potter ◽  
Eleanor M. Scott
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Potential ◽  
System Organization ◽  
Circadian System ◽  
Hierarchical System ◽  
Human Studies ◽  
Metabolic Abnormalities ◽  
System P ◽  
Key Aspects

Circadian (approximately 24-hour) rhythms are generated by a hierarchical system responsible for coordinating behaviour and physiology throughout the 24-hour day. Increasing evidence supports roles for disruption of the circadian system in the development of type 2 diabetes (T2DM) and depression. We outline the key aspects of circadian system regulation, discuss the findings indicating that biological disruption of the circadian system produces various behavioural and metabolic abnormalities, and review human studies which show that environmental disruption of the circadian system contributes to T2DM and depression. Finally, we will summarize the therapeutic potential of restoring circadian system organization to manage these diseases.

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