The anti-diabetic and insulin sensitizing potential of a watery extract of Agathosma tested in rat models of type 1 and type 2 diabetes

Jansen, Vereneque (2015-03)

Thesis (MSc)--Stellenbosch University, 2015.

Thesis

ENGLISH SUMMARY: Introduction: Epidemiological data highlights that South Africa is currently facing a quadruple burden of disease of which non-communicable diseases (NCDs) are estimated to account for 29% of all deaths. These NCDs include, amongst others, cardiovascular disease, type 2 diabetes, hypertension, cancer, chronic lung disease and depression. Diabetes has become a major problem worldwide and in South Africa and is currently rated as the 5th largest cause of death by Statistics South Africa in 2011. This creates an enormous burden of disease on populations and the utilization of herbal remedies has escalated in popularity because of this. Buchu water is one of these herbal remedies advertised as having anti-diabetic properties. This water is a by-product of the extraction of the oil from the leaves of Agathosma and is already freely available to the public. The aim of this study was therefore to use animal models of type 1 diabetes, and obesity and insulin resistance to scientifically verify or refute these claims. Methods: We utilized male Wistar rats. Two different rat models were used: (i) a type 1 diabetic model; induced via a once-off intraperitoneal Streptozotocin (40mg/kg) injection ablating ~50% of pancreatic beta cells (T1D); (ii) A diet-induced obese model, rendering rats insulin resistant after receiving a high caloric diet for 16 weeks. Half of each experimental group was treated with diluted Buchu water for a period of 14 weeks and 16 weeks, respectively, while the rest consumed normal water. Water and food consumption were monitored, body weight and intraperitoneal fat measured, blood was collected to determine serum glucose and insulin levels, skeletal muscle was removed to test insulin sensitivity using radiolabelled deoxyglucose, pancreas and skeletal muscle harvested and stored in liquid nitrogen for further biochemical analysis. Results: One of the main findings of this study was that ingestion of Buchu water results in weight loss despite no decrease in food consumption. This occurred in both the pathological models and control animals. In the obese animals, this weight loss was due to a decrease in intra-peritoneal fat. A second important finding was that the ingestion of Buchu water in all instances, whether given as treatment (treated with Buchu water 3 weeks after the start of the experiment) or as prophylactic (treated with Buchu water from the start of the start of the experiment), resulted in normalization of glucose levels in a type-1 diabetic model with residual beta-cell mass. An insulin-sensitizing effect was not clearly established in skeletal muscle but this may be because of a large variation in values obtained, as well as the use of a slow-twitch muscle. A definite effect on pancreatic insulin secretion has been demonstrated by raised C-peptide levels in the diet-induced obese model. Conclusion: This study, with regard to the type 1 diabetic model, has confirmed the anti-diabetic effect of Buchu water by significantly lowering blood glucose levels of fasted and non-fasted blood and normalizing Intraperitoneal glucose tolerance test (IPGTT) curves. This was however not so evident in the obese model utilized. Despite this, animals lost weight which was mainly intra-peritoneal fat.

AFRIKAANSE OPSOMMING: Inleiding: Epidemiologiese data dui aan dat daar tans ‘n viervoudige siektelading Suid Afrika in die gesig staar. Hiervan is nie-oordraagbare siektes (NCDs) vir ongeveer 29% van van sterftes verantwoordelik. Hierdie siektetoestande sluit kardiovaskulêre siektes, tipe 2 diabetes, hipertensie, kanker, kroniese longsiektes en depressie in. Diabetes is tans ook in Suid Afrika een van die groot gesondheidsprobleme en word deur die MNR 10de op die ranglys van oorsake van sterftes geplaas. Dit veroorsaak ‘n groot siektelas op die populasie in geheel. As gevolg hiervan het die gebruik van natuurlike produkte om siektes te behandel, geweldig toegeneem. Buchuwater is een so ‘n natuurlike produk wat geadverteer word om anti-diabetiese effekte te hê. Hierdie water is ‘n afvalproduk van die ekstraksie van Buchu-olie uit die blare van Agathosma en is alreeds vrylik aan die publiek beskikbaar. Metodes: Manlike Wistarrotte is vir die studie gebruik. Twee verskillende modelle is gebruik naamlik (i) ‘n tipe 1 diabetiese model daargestel deur ‘n enkele intraperitoneale Streptozotocin (40mg/kg) inspuiting waarmee ~50% van die betaselle van die pankreas vernietig word en (ii) ‘n dieet-geïnduseerde vetsugtige model waar rotte vir 16 weke op ‘n hoë kalorie dieet geplaas word. Helfte van elke eksperimentele groep diere se drinkwater is deur verdunde Buchuwater vervang vir die volle 16 weke. Water- en kosinname is gemonitor, liggaamsgewig en intraperitoneale vetgewig bepaal. Bloedglukose is gemonitor en intraperitoneale glukosetoleransie kurwes opgestel. Bloed is gekollekteer om serum insulienvlakke te bepaal en skeletspier insulienweerstandigheid is bepaal deur die opname van isotoopgemerkte deoksiglukose te meet. Pankreata is geoes en in vloeibare stikstof vir biochemiese analise gestoor. Resultate: Een van die hoofbevindinge van hierdie studie was dat die inname van Buchuwater gewigsverlies in diere teweeggebring het sonder dat hulle kosinname verminder het. Dit het in beide modelle, sowel in kontrol diere gebeur. In die vetsugtige diere was hierdie verlies as gevolg van verlies van intraperitoneale vet. ‘N tweede belangrike bevinding was dat die inname van Buchuwater ‘n normalisering van bloedglukosevlakke in die tipe 1 diabetiese diere met ‘n betasel reserwe teweeggebring het, beide wanneer dit as voorkomend of as behandeling gegee is. Sensitisering teenoor die effekte van insulin in die skeletspiere van die vetsugtige model rotte kon nie waargeneem word met die inname van Buchuwater nie, deels as gevolg van ‘n baie groot variasie in die resultate. Effekte van die Buchuwaterinname op die betaselle van die pankreas en insuliensekresie is gevind. Gevolgtrekking: Met betrekking tot die tipe 1 diabetiese model het die studie die antidiabetiese effekte van Buchuwater bevestig deur ‘n beduidende verlaging van vastende sowel as nie-vastende bloedglukosevlakke en normalisering van IPGTT kurwes teweeg te bring. Hierdie effekte was nie so voor die hand liggend in die vetsugtige model nie maar hierdie diere het gewig, hoofsaaklik intraperitoneale vet, verloof.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/96647
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