Interplay of Central and Peripheral Vascular Effects of Insulin in Obesity

• human insulin (Drug): Participants will be administered human insulin (160 IU) using an intra-nasal device.

Primary outcomes

• Amount of muscle sympathetic nerve activity (MSNA) [Change from baseline at minute 30]: MSNA burst incidence (bursts/100 heart beats)
• Amount of cerebral blood flow [Change from baseline at minute 30]: Measured with arterial spin labeling (mL/100 g/min)
• Amount of leg blood flow [Change from baseline at minute 30]: Measured with Doppler ultrasound (mL/min)

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* 18 to 65 years of age

Individuals with obesity and comorbid IR

* BMI 30-45 kg/m2
* Waist circumference ≥102 cm (men) or ≥88 cm (women)
* HOMA-IR ≥2.5

Healthy normal weight adults

* BMI 18-25 kg/m2
* Waist circumference <94 cm (men) and <80 cm (women)
* HOMA-IR <2

Exclusion Criteria:

* Pregnancy, breastfeeding
* Unable to provide consent
* Diabetes or polycystic ovarian syndrome
* Known history of cardiovascular disease: heart failure, ischemic heart disease, peripheral artery disease, stroke
* Nerve/neurologic disease
* Uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg)
* Active cancer (excluding basal cell carcinoma or stage 1 squamous cell carcinoma of the skin)
* Current smoking, tobacco, nicotine use
* Use of pharmacological therapy for weight loss
* Body weight change >10% within the last 6 months
* Adherence to >150 min/week of moderate-to-vigorous physical activity/exercise
* Participation in any other research study or medical procedure involving significant ionizing radiation exposure in the past 12 months
* Claustrophobia
* Non-MRI compatible metal implants