Female African Green Monkeys Exhibit Higher Insulin Sensitivity and Lower Blood Pressure than Age‐matched Males

Abstract

Type 2 Diabetes (T2DM) has become the most prevalent form of diabetes worldwide. In some studies, females have increased insulin sensitivity with greater glucose tolerance than males. Pre-menopausal females may also be protected from early onset T2DM, hypertension and early onset end stage renal disease. A subpopulation of African Green Monkeys (AGM; Chlorocebus aethiops sabaeus) exhibit spontaneous glucose intolerance and co-morbidities such as insulin insensitivity, and spontaneous hypertension. The AGM’ similarities to human pathologies make them an optimal experimental model for diabetes. Thus, we hypothesize that female AGM may differ in insulin sensitivity compared to age-matched males. Healthy, middle-aged AGM were utilized (n= 22 female, n=13 male). Systolic blood pressure (SBP) was measured by forearm plethysmography. Glucose tolerance was assessed via conscious and anesthetized oral glucose tolerance tests (OGTT). All AGM were fasted 12-18 hours with water provided ad libitum. Blood glucose was measured via standard glucometry at 0, 15, 30, 60, 90, and 120 min after an oral glucose load. Conscious AGM’ OGTT were delivered as 0.75g glucose/kg body weight. Anesthetized AGM (ketamine, 15mg/kg, i.m.), received 5g/dl glucose and 15 ml/kg in water. Venous blood samples were taken at 0, 30, 90 and 120 min after glucose administration in anesthetized AGM. All data between conscious and anesthetized OGTT were similar. All AGM were normotensive, however, male SBPs averaged 117.6 ± 4.2 mmHg compared with female SBPs of 104.1 ± 4.1 mmHg (p< 0.05). Female AGM area under the curve (AUC) for glucose was 12,102±466.9 min*mg/dl compared to 13,799.4±564.1 min*mg/dl for males over the 120 min after the glucose load. The peak blood glucose AUC response for females was 6,211.4 ± 219.5 min*mg/dl and 7,482 ±600.1 min*mg/dl in males (p<0.05). Insulin and C-peptide were also compared at the same time points. There were no differences in insulin or C-peptide responses between males and females. Overall renal glomerular function was assessed by measuring fasted, plasma creatinine concentrations. Average plasma creatinine was not different between males and females. These data demonstrate that middle-aged, males have decreased glucose tolerance compared to age-matched females despite similar OGTT induced changes in plasma insulin and C-peptide. Thus, middle-aged males have decreased insulin sensitivity in their response to glucose following an oral glucose load compared to females. All AGM in this study were normotensive however, females had significantly lower SBP than males, indicating that reduced glucose tolerance in males may contribute to elevated SBP. Together, the glucose and SBP data may suggest early onset of T2DM in males compared to age-matched females. This potential early onset T2DM has yet to induce overt alterations in renal glomerular filtration. Long-term studies are needed to assess whether further blood pressure elevation can lead to a decline in renal function and renal injury. Future studies will include differentiation of renal function in males and females including proteinuria, glomerular filtration, and kidney histology of AGM.