No description available.

Thesis advisor: Jason Kingsbury / Recent findings have led to the discovery that the Sc-catalyzed addition of substituted diazoalkanes to aldehydes elegantly affords a net carbon insertion into the C-H bond, delivering the requisite ketone in one simple step with no need for a readjustment in oxidation state. This chemistry is much improved over the century old diazomethane chemistry which requires stoichiometric amounts of a promoter and is limited in both application and scope. The new catalytic method has now been utilized as the key step in the synthesis of the pseduosymmetric precursor to the natural product achyrofuran, which has been named “pre-achyrofuran.” Subsequently, a related project was pursued involving the desymmetrization of bicyclic β-diketones by catalytic carbon insertion with trimethylsilyldiazomethane as the reagent. Preliminary developments in this area are disclosed. / Thesis (BS) — Boston College, 2010. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Chemistry Honors Program. / Discipline: Chemistry.

Thesis (MScMedSc (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Introduction: Obesity and its associated complications, such as the metabolic syndrome, hypertension and cardiovascular disease, are escalating worldwide. In recognition of this, untested remedies advertised as anti-diabetic agents are flooding the market. Many of these products have limited efficacy, limited tolerability and significant side-effects. One remedy, claiming to have anti-diabetic properties, is DiaviteTM. DiaviteTM, a herbal product, consisting solely of the dried and ground pods of the Prosopis glandulosa tree, which is currently marketed as a food supplement with blood glucose and blood pressure stabilizing properties, as well as having the ability to enhance glucose utilization. It is already freely available from agents as well as sold over the counter at pharmacies. The producers of DiaviteTM are now seeking registration for their product from the Medicines Control Council (MCC) and, therefore, require solid scientific evidence of its effects. Aims: The aims of our study were, on request of the producing company, to determine the efficacy of DiaviteTM (P. glandulosa) as an anti-diabetic agent and possible mechanisms of action of this plant product. Methology: We utilized rat models of streptozotocin (STZ)-induced type 1 diabetes and diet-induced obese (DIO) insulin resistance. Male Wistar rats were rendered (a) type 1 diabetic after a once-off intra-peritoneal injection of STZ at a dose of 40 mg/kg and (b) insulin resistant after being on a high caloric diet (DIO) for 16 weeks. Half the animals of the type 1 diabetes model as well as the insulin resistant model were placed on DiaviteTM treatment (25 mg/kg/day) for a period of 4 – 8 weeks, depending on the model. The STZ-induced type 1 diabetic rats were sacrificed and the pancreata harvested for histological analysis. Animals on the DIO diet were sacrificed and (i) intra-peritoneal fat weight determined (ii) isolated hearts subjected to ischaemia/reperfusion to determine infarct size and protein expression profiles and (iii) cardiomyocytes prepared to determine insulin sensitivity. At the time of sacrifice blood was collected for blood glucose and serum insulin level determination, for both models. In addition, a standard toxicology study was performed in Vervet monkeys over a 3 month period. Results: In our type 1 diabetic model (blood glucose > 10 mmol/L) with a β-cell reserve, DiaviteTM treatment lead to increased serum insulin levels (p < 0.001) in both control and STZ groups as well as increased small β-cell (0 - 2500 μm2) formation (p < 0.001) in the pancreas of the STZ animals. Hearts from DiaviteTM treated control and DIO insulin resistant animals presented with smaller infarct sizes (p < 0.05) after ischaemia/reperfusion compared to their controls. DiaviteTM treatment lead to the increase of basal (p < 0.01) and insulin-stimulated (p < 0.05) glucose uptake in cardiomyocytes prepared from DIO insulin resistant animals. DiaviteTM treatment also led to significantly suppressed PTEN expression and activity (p < 0.01) in the DIO insulin resistant animals. In addition, DiaviteTM treatment had (i) no obvious detrimental effects in our rat models and (ii) no toxicity over a 3 month period in vervet monkeys. Conclusion: Our present study has shown that DiaviteTM treatment lowers fasting blood glucose levels, stimulates insulin secretion and leads to the formation of β-cells. In addition, oral consumption of DiaviteTM elicits cardioprotection against an ischaemic incident. DiaviteTM treatment improves insulin sensitivity of cardiomyocytes. Furthermore, it has been established that DiaviteTM treatment has no obvious detrimental effects in either of our rat models and no short-term toxic effects over a 3 month period in Vervet monkeys (data not shown). We thus conclude that in our models, DiaviteTM proved safe and it seems as if DiaviteTM, after short-term use, is beneficial as a dietary supplement. / AFRIKAANSE OPSOMMING: Inleiding: Vetsug, en die gepaardgaande komplikasies, soos die metaboliese sindroom, hipertensie en kardiovaskulêre siektes, neem wêreldwyd toe. Daar is tans verskeie middels op die mark wat as anti-diabetiese middels geadverteer word. Baie van hierdie geadverteerde produkte het beperkte effektiwiteit en het verskeie newe-effekte. Een so ‘n middel, is DiaviteTM. DiaviteTM is 'n plantproduk, wat slegs uit die gedroogte en fyngemaakte peule van die P. glandulosa boom bestaan. Hierdie produk word tans bemark as 'n voedselaanvulling met beide bloedglukose en bloeddruk stabiliserende eienskappe, asook die vermoë om glukose gebruik te verbeter. DiaviteTM is reeds vrylik beskikbaar van agente sowel as verkrygbaar by verskeie apteke. Die produsente van DiaviteTM wil aansoek doen om registrasie vir hul produk by die Medisynebeheerraad (MCC) en hulle vereis daarom wetenskaplike bewyse van die gevolge van die gebruik van hierdie produk. Doel: Die doel van ons studie was om op versoek van die produksie maatskappy, die doeltreffendheid van DiaviteTM (P. glandulosa) as 'n anti-diabetiese behandeling te evalueer, sowel as die moontlike meganismes van werking van hierdie plantproduk. Metodes: Ons het gebruik gemaak van rot modelle van (i) streptozotocin (STZ)-geïnduseerde tipe 1 diabetes en (ii) dieet-geïnduseerde vetsugtig (DIO) insulienweerstandigheid. Manlike Wistar rotte was as (a) tipe 1 diabeties geklassifiseer na 'n eenmalige, intra-peritoneale inspuiting van STZ teen 'n dosis van 40 mg/kg en as (b) insulienweerstandig geklassifiseer, nadat hulle op 'n hoë kalorie dieet (DIO) vir 16 weke was. Die helfte van beide die tipe 1 diabetes en die insulienweerstandige groep diere was met DiaviteTM behandel (25 mg/kg/dag) vir 'n tydperk van 4 - 8 weke, afhangende van die model. Die STZ-geïnduseerde tipe 1 diabetes rotte is geslag en die pankreata geoes vir histologiese analise. Diere op die DIO dieet is geslag en (i) die intra-peritoneale vet gewig bepaal, (ii) die geïsoleerde harte blootgestel aan isgemie/herperfusie om die infarkt groottes vas te stel, sowel as die proteïenuitdrukkingsprofiele te bepaal en (iii) kardiomiosiete was berei om die insulien sensitiwiteit te bepaal. Ten tyde van die slagting is bloedmonsters geneem vir bloedglukose en serum insulien vlak bepaling, vir beide modelle. Additioneel, is 'n standaard toksologie studie met Vervet apies oor 'n 3 maande tydperk uitgevoer. Resultate: In die model van tipe 1 diabetes (bloed glukose > 10 mmol/L), met 'n β-sel reserwe, is gevind dat DiaviteTM behandeling tot verhoogde serum insulien vlakke (p < 0.001) in beide kontrole en STZ groepe lei. DiaviteTM behandeling lei ook tot ‘n hoër vlak van klein β-sel (0 - 2500 μm2) vorming (p < 0.001) in die pankreas van die STZ diere. Die harte van die DiaviteTM behandele kontrole en DIO groep het kleiner infarkt groottes (p < 0.05) getoon na isgemie/herperfusie in vergelyking met hul kontrole groepe. DiaviteTM behandeling het ook gelei tot verhoogde basal (p < 0. 01) en insulin-gestimuleerde (p < 0. 05) glukose opname in kardiomiosiete wat berei was van DIO insulinweerstandige diere. DiaviteTM behandeling het PTEN uitdrukking en aktiwiteit aansienlik onderdruk (p < 0.01) in die DIO insulienweerstandige groep diere. Daar is dus gevind dat DiaviteTM behandeling (i) geen duidelike nadelige invloed in ons rot-modelle en (ii) geen toksisiteit oor 'n 3 maande tydperk in Vervet apies getoon nie. Gevolgtrekking: Ons huidige studie toon dus dat DiaviteTM behandeling vastende bloedglukosevlakke verlaag, insulien sekresie stimuleer en die proses van β-sell vorming bevorder. Additioneel, is gewys dat wanneer DiaviteTM mondelings gebruik word, dit die hart beskerm teen isgemiese insidente. Ons het ook getoon dat DiaviteTM behandeling insuliensensitiwiteit van kardiomiosiete verhoog. Verder is daar vasgestel dat DiaviteTM behandeling geen ooglopende nadelige gevolge in beide ons rot-modelle getoon het nie en daar geen korttermyn-toksiese effekte oor 'n 3 maande tydperk in Vervet apies (data nie getoon) is nie. Ons kan dus aflei dat Diavite TM in ons modelle veilig is en na kort termyn gebruik, voordelig is as 'n dieetaanvulling.

Four plant species traditionally used for the treatment of diabetes by South African traditional healers and herbalists were investigated for hypoglycaemic activity. Species included Schkuhria pinnata (Lam.) Cabrera, Pteronia divaricata (P.J. Bergius) Less Elaeodendron transvaalense (Burtt Davy) R.H. Archer and Euclea undulata Thunb var. myrtina (Burch.) Hiern. Acetone and ethanol plant extracts were prepared and tested in vitro, for glucose utilization, at concentrations of 12.5 µg/ml on three cell lines namely; Murine C2C12 myocytes, Chang liver cells and 3T3-L1 preadipocytes. Metformin, at a concentration of 1 µM (0.166 µg/ml) was used as positive control for hepatic cells and insulin at a concentration 1 µM (5.7 µg/ml) for myocytes and preadipocytes. Toxicity tests were done for all extracts on preadipocytes and hepatic cells, but not on myocytes as these cells were exposed to the extract for only a short period (1 hour) during the hypoglycaemic bioassay. Preadipocytes and hepatic cells were exposed to the plant extracts for 48 hours. The four plant extracts were further investigated for hypoglycaemic activity by evaluating inhibiting effects on carbohydrate-hydrolising enzymes alpha-glycosidase and alpha-amylase. In vitro hypoglycaemic analysis revealed that acetone and ethanol plant extracts of S. pinnata, E. undulata and E. transvaalense, displayed hypoglycaemic activity in one or more of the various cell lines, whereas, P. divaricata showed no hypoglycaemic activity. The best results were obtained with the ethanol and acetone extracts of S. pinnata in preadipocytes with a glucose uptake of 148.2% and 79.6% respectively, above control (100%). However, about 50% preadipocytes survived on exposure to the extracts of S. pinnata at 12.5 µg/ml indicating significant cytotoxicity. Glucose uptake of 63.3% was observed by the ethanol extract of S. pinnata on hepatic cells. E. transvaalense showed hypoglycaemic activity on preadipocytes exhibiting glucose uptake of 38.6% above control 100%. Glucose uptake of 62.2 % were obtained by the E. undulata extract in C2C12 myocytes, with 100% cell viability. E. undulata scored a +3 and was chosen for further analysis. Antidiabetic activity and toxicity of the plant extracts were taken into consideration when scoring was applied. Alpha-glucosidase and alpha-amylase results indicated that P. divaricata extract inhibited alpha-glucosidase (IC50 31.22 µg/ml) whereas E. undulata (IC50 2.80 µg/ml) and E. transvaalense (IC50 1.12 µg/ml) extracts inhibited alpha-amylase. Results obtained indicated that all four plant extracts tested have the ability to lower blood glucose levels to some extent and in different manners and therefore corroborate the ethnomedicinal use of these four species in the treatment of diabetes. Phytochemical studies of a crude acetone extract of the root bark of E. undulata var. myrtina produced a new á-amyrin-3O-β-(5-hydroxy) ferulic acid compound (1), and three known compounds; betulin (2), lupeol (3) and epicatechin (4). The chemical structures were determined by spectroscopic means. In vitro assays on C2C12 myocytes revealed that (2) (21.4%) and (4) (166.3%) were active in lowering blood glucose levels whereas (1) (IC50 4.79 µg/ml) and to a lesser extent (4) (IC50 5.86 µg/ml) and (3) (IC50 6.27 µg/ml) inhibited alpha-glucosidase. These results indicated that the crude, E. undulata acetone extract does contain compounds that display hypoglycaemic activity. The hypoglycaemic activity of four plant species including E. undulata, and the four isolated purified compounds, are reported for the first time. / Thesis (PhD)--University of Pretoria, 2010. / Plant Science / unrestricted

Global food and nutritional insecurities, public health challenges of diet-linked non-communicable chronic diseases (NCDs), and rapid climate change-linked agricultural production challenges are interconnected and require urgent attention. Therefore, to address these complex and interconnected challenges, it is essential to advance robust and resilient strategies based on sustainable agricultural production practices, wider integration of nutritionally-balanced plant-based foods in the diet, improvement of human health-targeted nutritional qualities, post-harvest preservation qualities and food processing optimization. Therefore, food plants that are climate resilient and rich source of human health protective nutritional bioactives, such as sweet potato are ideal dietary targets for advancing global food and nutritional security solutions, while also addressing emerging NCD-linked health challenges. Sweet potatoes are rich source of stress protective phenolic bioactives with dual functional benefits relevant for resilience to climate change and countering diet-linked NCD challenges. However, the phenolic bioactive compounds and associated health protective functionalities of sweet potatoes vary widely between different flesh color and cultivars, due to different pre-harvest production practices, post-harvest storage conditions, and with different food processing strategies. Therefore, the aim of this dissertation was to screen sweet potato cultivars of different flesh color (off-white, orange, purple) and optimizing different food processing strategies based on optimum phenolic bioactive-linked antioxidant, anti-diabetic and anti-hypertensive properties using metabolically-targeted in vitro assay models. Overall, high soluble phenolic-linked antioxidant activity was observed in purple-fleshed cultivar, while high type 2 diabetes relevant anti-hyperglycemic and anti-hypertensive properties were observed in orange and white-fleshed sweet potatoes. Additionally, improvement in stability and retention of phenolic bioactives and associated functionalities were present in bio-transformed sweet potatoes after fermentation with beneficial lactic acid bacteria (LAB). Furthermore, food processing (deep-frying, baking, steaming, and boiling) optimization studies revealed optimum food processing conditions (cooking temperature, cooking time, and sweet potato sample size) based on higher retention of phenolics and associated antioxidant and anti-hyperglycemic functionalities. We also advanced metabolically-driven elicitation strategy based on the conceptual foundation of dual functional benefits of phenolic compounds to improve wound-healing in bruised potato tubers through stimulation of redox-linked pathway (pentose phosphate pathway) regulation associated with stress-protective phenolic biosynthesis and antioxidant enzyme responses.

No description available.

Diabetes mellitus is the most well-known endocrine dilemma suffered by hundreds of million people globally, with an annual mortality of more than one million people. This high mortality rate highlights the need for in-depth study of anti-diabetic agents. This review explores the phytochemical contents and anti-diabetic mechanisms of (cucurbitaceae). Studies show that contains several phytochemicals that have hypoglycemic effects, thus, the plant may be effective in the treatment/management of diabetes mellitus. Also, the biochemical and physiological basis of anti-diabetic actions is explained. exhibits its anti-diabetic effects via the suppression of MAPKs and NF-κβin pancreatic cells, promoting glucose and fatty acids catabolism, stimulating fatty acids absorption, inducing insulin production, ameliorating insulin resistance, activating AMPK pathway, and inhibiting glucose metabolism enzymes (fructose-1,6-bisphosphate and glucose-6-phosphatase). Reviewed literature was obtained from credible sources such as PubMed, Scopus, and Web of Science.

Magister Public Health - MPH (Public Health) / The prevalence of diabetes in Africa has been on the increase. A prevalence of 1%- 10% has been reported by different authors in different regions in Nigeria. The International Diabetes Federation estimates that 1.9% of Nigerians are diabetic and most of them have complications at the time of diagnosis. Laboratory measurement of Glycosylated hemoglobin (HbA1c) is the method of choice for monitoring glycaemic control but due to its cost and limited availability, most developing countries use fasting plasma glucose (FPG) measurement (which is less reliable) to assess glycaemic control. Most diabetic patients in Nigeria have poor glycaemic control and several factors have been implicated especially socio-economic, behavioral and treatment-related factors. Understanding the reasons for poor glycaemic control is essential in order to reduce the rate of diabetes complications.

The biochemical factors affecting post-harvest preservation in apples indicated that well-preserved varieties of apples had increased superoxide dismutase (SOD) activity initially and the activity declined during later storage as apples deteriorated. The SOD link to better preservation correlated with higher phenolic content and free-radical scavenging linked antioxidant activity. Well-preserved varieties were able to maintain a more stable pentose phosphate pathway (PPP) (measured by the activity of glucose-6-phosphate dehydrogenase, G6PDH) throughout the storage period. Proline content increased in all varieties with an increase in proline dehydrogenase (PDH) activity in the initial period indicating proline catabolism supporting potential ATP synthesis. During later storage succinate dehydrogenase (SDH) activity increased while PDH activity declined indicating a shift to tricarboxylic acid cycle and likely NADH generation for ATP synthesis. This shift coupled with the declining SOD activity coincides with rapid deterioration. The guaiacol peroxidase activity (GPX) activity generally declined in late stages indicating post-harvest deterioration. Increasing number of studies have shown that regular intake of fruits and vegetables have clear links to reduced risk of chronic diseases like diabetes and cardiovascular disease. The beneficial effects in many cases have been attributed to the phenolic and antioxidant content of the fruits and vegetables. Apples are a major source of fiber and contain good dietary phenolics with antioxidant function. Previous epidemiological studies have indicated that intake of apples reduces the risk of developing Type II diabetes. Our studies indicate that this reduced risk is potentially due to modulation of postprandial glucose increase by phenolics present in apples via inhibition of a-glucosidase. Phenolic content was evaluated during 3 months of post-harvest storage of four varieties of apples and results indicated positive linkage to enhanced post-harvest preservation and a-glucosidase inhibition. These in vitro results along with existing epidemiological studies provide strong biochemical rationale for further animal or human clinical studies.

Impaired endothelial vasomotor function is a hallmark of many chronic disease states, including essential hypertension and type 2 diabetes mellitus. Loss of the homeostatic role of the endothelium in large conduit arteries can contribute to the pathogenesis of cardiovascular conditions in these vessels (e.g. stroke, atherosclerosis). A fundamental understanding of mechanisms controlling endothelial function in hypertension and type 2 diabetes mellitus is required for appropriate clinical strategies targeting the cardiovascular conditions associated with these diseases. The vast majority of basic science studies examining endothelial function in animal models of hypertension and type 2 diabetes have been conducted in males. Studying endothelial function in females is imperative for determining potential sex-specific mechanisms of dysfunction and thus appropriate therapeutic strategies. Thus the global purpose of this thesis is to identify and characterize the pathways controlling impaired vasomotor function in female animal models of two chronic disease states: hypertension and type 2 diabetes mellitus. Chapters 2 and 3 of this thesis examine sex differences in endothelium-dependent vasorelaxation (EDR) and vasocontraction (EDC) of aortic segments isolated from male and female spontaneously hypertensive rats (SHR), a model of essential hypertension, as the animals age between 16 and 30 wk old. All endothelial vasomotor data presented in the Abstract are peak responses to 10⁻⁵ M acetylcholine. Endothelial vasomotor impairment is represented by lower EDR or by higher EDC. These present data confirmed well-established findings from the literature that 16 wk old male SHR exhibit endothelial vasomotor impairments (EDR: 77±4 %; EDC: 76±7 %) compared to normotensive Wistar-Kyoto (WKY; EDR: 89±6 %; EDC: 59±8 %; p<0.05) controls, and that this impairment worsens with ageing in 30 wk male SHR (EDR: 63±2 %; EDC: 91±3 %; p<0.05). The observation that EDR was reduced in 30 wk female SHR (EDR: 76±4 %) compared to 16 wk counterparts (EDR: 101±2 %; p<0.05), however, was novel and interesting, as there were previously no reports of vasomotor responses in female SHR older than 19 wk. Moreover, the blunted EDR response of 30 wk female SHR approached the level of impairment exhibited by 30 wk male SHR (but was still slightly greater in females; p<0.05). The limited sex difference of the EDR within 30 wk SHR (males –13 % vs. females; p<0.05) contrasted that of 16 wk SHR (males –24 % vs. females; p<0.05), when the robust and unimpaired relaxation displayed by females was much greater than the significantly blunted response of males. Interestingly, endothelium-dependent contractions in quiescent rings were moderate and similar between 16 wk (EDC: 50±4 %) and 30 wk female SHR (EDC: 59±7 %; p=N/S) as compared to the greater contractions of males that were exacerbated with ageing (see above; p<0.05 both sex and ageing comparison). A major role has been established for the cyclooxygenase (COX)-1-thromboxane A₂/prostaglandin (TP) receptor pathway in the impaired endothelial vasomotor function of male SHR. Indeed, a similar mechanism appears to be responsible for the dysfunction observed in 30 wk female SHR in this thesis since robust endothelial function was restored in these animals with both antagonism of TP receptor (EDR: 111±2 %; EDC: 7±2 %; p<0.05) and preferential inhibition of COX-1 (EDR: 112±3 %; EDC: –5±3 %; p<0.05). In contrast, preferential inhibition of COX-2 only partially tempered endothelial impairments of 30 wk female SHR (EDR: 99±5 %; EDC: 27±3 %; p<0.05), suggesting that, similar to ageing male SHR, this isoform makes at most a secondary contribution to the dysfunction in 30 wk female SHR. Collectively, these data indicate that ageing female SHR exhibit a mechanism of endothelial impairment that is similar to that of male SHR and that is largely COX-1- and TP receptor-dependent. Chapter 4 examines the ability of chronic dietary administration of the n-3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA, 22:6 n-3), to ameliorate endothelial vasomotor function in adult male SHR with established hypertension. The impaired endothelial function of aortic segments isolated from adult male SHR (EDR: 48±6 %) was not improved following 10–12 wk of DHA feeding (EDR: 45±5 %; p=N/S). This finding was unexpected since it has been shown in the literature that feeding other n-3 PUFAs improves vasomotor responses in younger SHR, in which hypertension and its associated consequences are still developing. This is the first report of the effects of n-3 PUFA on endothelial vasomotor responses in adult SHR with established hypertension. These data suggest that dietary DHA do not improve vasomotor function in adult SHR. Chapter 5 examines α₁ adrenergic contraction and EDR of aortic segments isolated from 14 wk old female Zucker diabetic fatty rats (ZDF), a genetic model of high fat diet-induced obesity and type 2 diabetes, and lean non-diabetic female Zucker Lean rats. Additionally, some ZDF received an 8 wk administration of anti-diabetic metformin drug therapy, aerobic exercise training, or a combination of the two. Maximal α₁ adrenergic contractions were over 2-fold higher in high fat-fed ZDF (1.69±0.16 g) compared to Lean (0.71±0.13 g; p<0.05). This elevation in ZDF was abolished by exercise training alone (1.02±0.17 g; p<0.05) but was not altered by metformin (1.56±0.19 g; p=N/S). In contrast to the severely impaired endothelial vasomotor function reported in male ZDF in the literature, robust EDR was observed in female ZDF (72±7 %) that was similar to Lean (75±6 %; p=N/S) and that was unaltered by exercise training (76±5 %; p=N/S) or metformin (76±6 %; p=N/S). These results indicate that enhanced α₁ adrenergic contraction is a mechanism of altered vasomotor function in female type 2 diabetic ZDF rats and that it could possibly be addressed by a chronic exercise training intervention. The main novelty of the thesis is the extension of the current understanding of endothelial vasomotor function to hypertensive and type 2 diabetic females. The knowledge gained from examining mechanisms involved in endothelial impairments in ageing hypertensive females and from testing the therapeutic potential of currently used anti-diabetic interventions in the type 2 diabetic female vasculature has interesting potential application. This basic scientific information could help direct clinical therapeutic strategies to target population-specific mechanisms of dysfunction. Understanding female sex-specific endothelial behaviour in patient populations is important for describing cardiovascular complications, defining mechanisms, and applying appropriate therapeutic targets. Findings from this thesis indicate a sex-dependence of the total divergence of endothelial function (e.g. female type 2 diabetic rats vs. male counterparts in the literature) and of the interaction of disease variables (e.g. age) and endothelial vasomotor responses.