Biology subjects

Moore, M. C.

Publications and source records attributed to Moore, M. C..

3 recordsLinked to original sources

bioRxiv2024

Morning Engagement of Hepatic Insulin Receptors Improves Afternoon Hepatic Glucose Disposal and Storage

Glucose tolerance improves significantly upon consuming a second, identical meal later in the day (second meal phenomenon). We previously established that morning hyperinsulinemia primes the liver for increased afternoon hepatic glucose uptake (HGU). Although the route of insulin delivery is an important determinant of the mechanisms by which insulin regulates liver glucose metabolism (direct hepatic vs indirect insulin action), it is not known if insulins delivery route affects the second meal response. To determine whether morning peripheral insulin delivery (as occurs clinically (subcutaneous)) can enhance afternoon HGU, conscious dogs were treated in the morning with insulin delivered via the portal vein, or peripherally (leg vein), while glucose was infused to maintain euglycemia. Consequently, arterial insulin levels increased similarly in both groups, but relative hepatic insulin deficiency occurred when insulin was delivered peripherally. In the afternoon, all animals were challenged with the same hyperinsulinemic-hyperglycemic clamp to simulate identical postprandial-like conditions. The substantial enhancement of HGU in the afternoon caused by morning portal vein insulin delivery was lost when insulin was delivered peripherally. This indicates that morning insulin does not cause the second meal phenomenon via its indirect actions on the liver, but rather through direct activation of hepatic insulin signaling. Article HighlightsO_LIMorning insulin delivery primes the liver for increased hepatic glucose uptake (HGU) later in the day, but the mechanism (direct hepatic and/or indirect insulin action) remains unclear. C_LIO_LIThis study compared insulin infusion via physiologic (hepatic portal vein) and clinical (peripheral) routes to assess their impact on afternoon hepatic glucose disposal. C_LIO_LIMorning peripheral insulin delivery failed to induce a significant enhancing effect on afternoon HGU and glycogen storage, unlike morning hepatic portal vein insulin delivery, which did. C_LIO_LIThese findings highlight the importance of achieving appropriate hepatic insulin exposure in the morning to effectively prime the liver for efficient glucose disposal. C_LI

physiology↗

bioRxiv2024

Duration of Morning Hyperinsulinemia is Key to the Enhancement of Hepatic Glucose Uptake and Glycogen Storage Later in the Day

The second meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 hours of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, we administered the same total amount of insulin either over 2h in the first (Ins2h-A) or second (Ins2h-B) half of the morning, or over the entire 4h (Ins4h) of the morning. In the 4h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared to the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp. New and noteworthyMorning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulins ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.

physiology↗

bioRxiv2023

A High-Fat and Fructose Diet in Dogs Mirrors Insulin Resistance and β-cell Dysfunction Characteristic of Impaired Glucose Tolerance in Humans

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and {beta}-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the {beta}-cells capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.

physiology↗