Insulin- and glucagonlike peptides in the brain

Area of Science:

• Neuroscience
• Endocrinology
• Biochemistry

Background:

• Insulin and glucagon are key metabolic hormones primarily associated with the pancreas.
• Their presence and function within the central nervous system (CNS) are not fully understood.
• Investigating their localization and potential endogenous production in the brain is crucial for understanding neuroendocrinology.

Purpose of the Study:

• To investigate the cellular localization and regional distribution of insulin, glucagon-like substance, C-peptide, thiol:protein disulphide oxidoreductase (TPO), and insulin/glucagon-specific proteinase (ISP) in the CNS of various species.
• To quantify the levels of immunoreactive insulin, glucagon, and C-peptide in human brain tissue.
• To determine if the brain produces its own insulin and glucagon.

Main Methods:

• Immunohistochemistry was used to study the distribution of immunoreactive substances in the CNS of humans, rats, mice, tortoises, and frogs.
• Radioimmunoassay was employed to measure the content of immunoreactive insulin, glucagon, and C-peptide in human cadaver brains.
• Specific antisera were used to differentiate between gut-type and pancreas-type glucagon.

Main Results:

• Insulin-like immunoreactivity was widely distributed in the human brain and juvenile rat/mouse CNS, but restricted in adult rat and non-mammalian CNS.
• C-peptide immunoreactivity colocalized with insulin in human CNS neurons.
• Gut-type glucagon was found in many nerve cells of human, mouse, and juvenile rat brains, while pancreas-type glucagon was less prevalent.
• Thiol:protein disulphide oxidoreductase (TPO) and insulin/glucagon-specific proteinase (ISP) were detected in the brain, indicating degradation capabilities.
• Human brain tissue contained higher concentrations of insulin, glucagon, and C-peptide than blood levels.

Conclusions:

• The human brain contains insulin, glucagon, and C-peptide at levels higher than in circulation.
• The presence of TPO and ISP suggests nervous tissue can degrade insulin and glucagon.
• Cerebral insulin and glucagon are, at least in part, produced within the brain itself.