Abstract:There was no demonstrable priming effect derived from overnight pulsatile insulin compared with constant insulin infusion on subsequent insulin sensitivity in Type 2 diabetic subjects. The failure of 7-min pulses to exhibit an advantageous effect over 13-min pulses raises questions about the natural frequency of basal insulin pulses and their biological effect.
“…Studies in animal models have suggested that pulsatile insulin delivery is superior in suppressing hepatic glucose output than continuous insulin administration . Studies comparing pulsatile vs. continuous insulin administration in humans are controversial , which might in part be explained by the fact that the endogenous route of intraportal insulin delivery cannot readily be mimicked by peripheral intravenous (i.v.) insulin administration.…”
Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous β-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.
“…Studies in animal models have suggested that pulsatile insulin delivery is superior in suppressing hepatic glucose output than continuous insulin administration . Studies comparing pulsatile vs. continuous insulin administration in humans are controversial , which might in part be explained by the fact that the endogenous route of intraportal insulin delivery cannot readily be mimicked by peripheral intravenous (i.v.) insulin administration.…”
Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous β-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.
“…Other studies have investigated the effect of overnight pulsatile versus continuous basal insulin infusions on insulin action measured during a clamp test administered in the morning. In subjects with and without diabetes, they found no priming effect of basal pulsatile insulin on glucose uptake during the clamp 68,69 …”
Section: Effects Of Pulsatile Insulin Secretion On Insulin Actionmentioning
confidence: 94%
“…In subjects with and without diabetes, they found no priming effect of basal pulsatile insulin on glucose uptake during the clamp. 68,69 On the other hand, the importance of the pulsatile release pattern in regulating physiologic insulin action can be appreciated from experimental models demonstrating that the response of key phosphorylation events in the insulin signaling cascade in the fed state are robust when primed by fasted insulin pulses. It appears that pulses in the fasted state create a memory that sensitizes the signaling in the fed state.…”
Section: Effects Of Pulsatile Insulin Secretion On Insulin Actionmentioning
SummaryInsulin 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.
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