Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance.

Summary

Glucagon secretion from α-cells has long been viewed as primarily a counterregulatory mechanism - e.g. an agent with a role to prevent blood sugar from decreasing to levels that compromise function. Our group, along with other researchers, have begun to identify a much more complex role for α-cells, raising questions about when and how glucagon may influence blood glucose levels. This proposal looks to detail proglucagon peptide secretion from α-cells and the impact this has on β-cell function and glucose tolerance, in preclinical studies of human islets and translational studies in human subjects. This protocol registration describes Aim 2 from this NIH grant which involves 2 study populations and separate protocols but addresses a common question. Aim 3 in the grant is focused on a separate hypothesis and will be conducted and published separately from Aim 2.

Eligibility

Aim 2A: Inclusion Criteria:

* Age 18-45
* Body Mass Index (BMI) \< 27.0
* Fasting plasma glucose of ≤ 95 mg/dL or HbA1c value ≤ 5.8% as measured at screening visit

Exclusion Criteria:

* Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders
* Personal history of diabetes or pancreatitis
* Personal history of cardiac, gastrointestinal, renal or liver disease
* Immediate family history of diabetes
* Renal insufficiency (eGFR \< 60 mL/kg/min)
* Anemia (hematocrit \< 34%) as measured at screening visit
* Pregnant females
* Poor vein access
* Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
* Apparent sensitivity to the study peptide as determined by the skin test

Aim 2B: Inclusion Criteria:

* Age 35-60
* Body Mass Index (BMI) ≥ 27.0
* Fasting plasma glucose of \< 126 mg/dL or HbA1c value \< 6.5% as measured at screening visit

Exclusion Criteria:

* Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders
* Personal history of diabetes or pancreatitis
* Personal history of cardiac, gastrointestinal, renal or liver disease
* Immediate family history of diabetes
* Renal insufficiency (eGFR \< 60 mL/kg/min)
* AST and/or ALT levels \> 3x the upper limit of the normal range
* Anemia (hematocrit \< 34%) as measured at screening visit
* Pregnant females
* Poor vein access
* Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide)
* Apparent sensitivity to the study peptide as determined by the skin test

Conditions2

Locations1 site

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