Insulin is secreted in pulses from pancreatic beta-cells, and these oscillations maintain fasting plasma glucose levels within a narrow normal range. Within islets, beta-cells exhibit tight synchronization of regular oscillations. This control circuit is disrupted in type 2 diabetes, and irregularities in pulse frequency and amplitude occur. The prevalence of type 2 diabetes is three times higher in American Indian and Native Alaskans compared to Whites, and their genetic ancestry is associated with low beta-cell function. Obesity in this population compounds their vulnerability to adverse outcomes. The purpose of this article is to review insulin secretion and action and its interaction with race. We also present the results from a 6-month retrospective chart review of metabolic outcomes following intravenous physiologic hormone administration to 10 Native Americans. We found reductions in hemoglobin A1C (baseline: 9.03% ± 2.08%, 6 months: 7.03% ± 0.73%, p = 0.008), fasting glucose (baseline: 176.0 ± 42.85 mg/dL, 6 months: 137.11 ± 17.05 mg/dL, p = 0.02), homeostatic model assessment of insulin resistance (baseline: 10.39 ± 4.66, 6 months: 7.74 ± 4.22, p = 0.008), and triglycerides (baseline: 212.20 ± 101.44, 6 months: 165.50 ± 76.48 mg/dL, p = 0.02). Physiologic hormone administration may improve components of the metabolic syndrome. The therapy warrants investigation in randomized controlled trials.