- Title
- The inhibitory effects of cannabinoids from cannabis sativa on the enzymes dipeptidyl peptidase-IV, sucrase and maltase as a new therapeutic treatment for type 2 diabetes
- Creator
- Viljoen, Zenobia
- Subject
- Diabetes -- Treatment
- Subject
- Cannabinoids -- Therapeutic use
- Subject
- Medical Marijuana -- therapeutic use
- Date Issued
- 2024-12
- Date
- 2024-12
- Type
- Master's theses
- Type
- text
- Identifier
- http://hdl.handle.net/10948/69516
- Identifier
- vital:77264
- Description
- Type 2 diabetes is one of the most prevalent diseases worldwide. The treatments used to manage diabetes often have severe side effects and patients develop resistance to traditional treatment. The project aimed to test if phytocannabinoids from Cannabis sativa inhibited key enzymes involved in glycaemic homeostatic regulation, namely dipeptidyl peptidase 4 (DPP-4), sucrase, and maltase. This study investigated the inhibitory effects of 3 M-128 M cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9- tetrahydrocannabinol (THC). CD spectroscopy was used to investigate the changes in the secondary structure of DPP-4 with interacting inhibitors. The effect of 1.25, 2.5, and 5 mg/kg rat THC cannabis extract on the activity of DPP-4 in blood plasma and rat pancreatic tissue of the diabetic rat model and obese rat model. The effect of 1.25, 2.5, and 5 mg/kg rat THC cannabis extract on glucagon concentration in the blood plasma of the diabetic rat model and obese rat model was investigated. The carbohydrate digestive enzymes namely -amylase, -glucosidase and maltase are not inhibited by any of the cannabinoids. CBN had inhibitory effects on sucrase. CBN, CBG, and CBD are mixed inhibitors of DPP-4, thus they can inhibit DPP-4 competitively and uncompetitively depending on the concentration of the cannabinoid. THC was shown in kinetic and rat model studies to be a very weak inhibitor of DPP-4. CD spectroscopy showed that sitagliptin (FDA-approved drug and competitive inhibitor) and CBG mimic the denatured structure of DPP-4. CBD, CBN and THC mimic the free (active) form of DPP-4. A reduction in pancreatic DPP-4 activity was observed with 2.5 and 5 mg/kg rat THC (diabetic model). This study showed that diet plays a role in glycaemic dysregulation (obese rat model) and that insulin-resistant rats had four times higher glucagon levels compared to the lean control (diabetic model). 1.25 mg/kg rat THC reduced blood plasma DPP-4 activity and blood plasma glucagon. Cannabis sativa can be a feasible treatment to help manage type 2 diabetes by inhibiting DPP-4, especially medical strains of Cannabis sativa with high concentrations of CBD and CBG.
- Description
- Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 2024
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (107 pages)
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
- Rights
- All Rights Reserved
- Rights
- Open Access
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Collections
NMU School of BioMolecular and Chemical Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | VILJOEN, Z.pdf | 1 MB | Adobe Acrobat PDF | View Details Download |