I loko o ka pancreas, hui pū ʻia nā cell beta e hana ana i ka insulin me nā ʻāpana endocrine hana ʻē aʻe a hoʻopuni ʻia e nā cell exocrine pancreatic e hūnā i nā enzyme digestive. Ua hōʻike nā mea noiʻi ʻo Joslin Diabetes Center i ke ʻano o kahi ʻano o ka maʻi hoʻoilina i ʻike ʻia ʻo ka maʻi diabetes o ka wā ʻōpio (MODY) e alakaʻi ʻia e nā enzyme digestive mutated i hana ʻia i loko o nā cell exocrine pancreatic a laila lawe ʻia e nā pūnae beta huna huna insulin.
Hiki i kēia ʻike ke kōkua i ka hoʻomaopopo ʻana i nā maʻi ʻē aʻe o ka pancreas, e komo pū ana me ka maʻi diabetes type 1 a i ʻole type 2, kahi e hana ʻino ai ka molecular crosstalk ma waena o kēia mau pūʻulu ʻelua, wahi a ka mea noiʻi nui ʻo Joslin ʻo Rohit N. Kulkarni, MD, PhD, ʻO ke poʻo o ka ʻāpana hui o Joslin's Islet a me Regenerative Biology Section a me kahi Kauka Lapaʻau ma Harvard Medical School.
ʻO ka hapa nui o ka MODY ke kumu o ka hoʻololi ʻana i nā genes e hōʻike ana i nā protein i loko o nā pūnae beta. Akā ma kekahi ʻano o MODY i kapa ʻia ʻo MODY8, ʻike ʻia kahi ʻano mutated i nā cell exocrine kokoke e hoʻomaka i kēia kaʻina hana ʻino, wahi a Kulkarni, ka mea kākau pili ma kahi pepa Nature Metabolism e hōʻike ana i ka hana. Ua ʻike ka poʻe ʻepekema i kāna lab ma MODY8, nā enzyme digestive i hana ʻia e kēia ʻano gene mutated aggregate i loko o nā cell beta a hōʻino i ko lākou olakino a me ka hana hoʻokuʻu insulin.
"ʻOiai ʻo ka endocrine a me ka exocrine pancreas e hoʻokumu i ʻelua mau ʻāpana me nā hana ʻokoʻa, ʻo kā lākou pilina anatomical pili e hoʻohālikelike i ko lākou hopena," wahi a Sevim Kahraman, PhD, kahi mea noiʻi postdoctoral ma ka Kulkarni lab a me ke alakaʻi kumu o ka pepa. "ʻO ke kūlana pathological e ulu ana ma kekahi ʻāpana e hōʻino i kekahi."
"ʻOiai he maʻi kakaikahi loa ka MODY8, hiki ke hoʻomālamalama i nā hana maʻamau e pili ana i ka ulu ʻana o ka maʻi maʻi maʻi," wahi a Anders Molven, PhD, he mea kākau a me ke Kumu ma ke Kulanui o Bergen ma Norewai. "Ke hōʻike nei kā mākou ʻike i ke ʻano o ke kaʻina hana maʻi e hoʻomaka ana i ka pancreas exocrine i ka hopena i ka hopena o nā pūnaewele beta e hana nei i ka insulin. Manaʻo mākou e pili pono ana kēlā ʻano exocrine-endocrine crosstalk no ka hoʻomaopopo ʻana i kekahi mau hihia o ka maʻi diabetes type 1.
Ua wehewehe ʻo Kulkarni, ʻo ke ʻano CEL (carboxyl ester lipase) i hoʻololi ʻia ma MODY8, ua manaʻo ʻia he gene pilikia no ka maʻi diabetes type 1. ʻO ia ka mea e hāpai ai i ka nīnau inā paha e hōʻike pū kekahi mau hihia o ka maʻi diabetes type 1 i kēia mau protein mutant aggregated i nā cell beta, i ʻōlelo ai ʻo ia.
Ua hoʻomaka ke aʻo ʻana ma ka hoʻololi ʻana i kahi laina cell exocrine (acinar) kanaka e hōʻike i ka mutant CEL protein. I ka wā i ʻauʻau ʻia ai nā pūnaewele beta i ka hoʻonā ʻana mai nā cell exocrine maʻamau a i ʻole mutated, ua lawe nā beta cell i nā protein mutated a me nā protein maʻamau, e lawe mai i nā helu kiʻekiʻe o nā protein mutated. Ua hoʻohaʻahaʻa ʻia nā protein maʻamau e nā kaʻina hana maʻamau i loko o nā pūnae beta a nalowale i nā hola he nui, akā ʻaʻole naʻe nā protein mutant, ma kahi o ka hoʻokumu ʻana i nā protein aggregates.
No laila pehea i hoʻopili ai kēia mau hōʻuluʻulu i ka hana a me ke olakino o nā cell beta? Ma ke ʻano o nā hoʻokolohua, ua hōʻoia ʻo Kahraman a me kāna mau hoa hana ʻaʻole huna nā cell i ka insulin e like me ke koi ʻana, hoʻonui mālie a ʻoi aku ka maʻalahi o ka make.
Ua hōʻoia ʻo ia i kēia mau ʻike mai nā laina kelepona me nā hoʻokolohua i nā cell mai nā mea hāʻawi kanaka. Ma hope aʻe, ua hoʻololi ʻo ia i nā cell exocrine kanaka (e hōʻike hou ana i ka mutated a i ʻole ka digestive enzyme maʻamau) me nā cell beta kanaka i loko o kahi kiʻi ʻiole i hoʻolālā ʻia e ʻae i nā cell kanaka. "ʻOiai i loko o kēlā hiʻohiʻona, hiki iā ia ke hōʻike i ka lawe hou ʻia ʻana o ka protein mutated e ka beta cell i ka hoʻohālikelike ʻana i ka protein maʻamau, a hana ia i nā aggregates insoluble," wahi a Kulkarni.
Eia kekahi, i ka nānā ʻana i nā pancreas mai ka poʻe me MODY8 i make mai nā kumu ʻē aʻe, ua ʻike nā mea noiʻi aia i loko o nā cell beta ka protein mutated. "Ma nā mea hāʻawi olakino, ʻaʻole mākou i ʻike i ka protein maʻamau i loko o ka cell beta," wahi āna.
"Ua hoʻomaka mua kēia moʻolelo MODY8 me ka nānā ʻana i nā maʻi me ka maʻi maʻi me nā pilikia digestive, i alakaʻi ai i ka loaʻa ʻana o kahi denominator genetic maʻamau," wahi a Helge Raeder, MD, he mea kākau a me ke Kumu ma ke Kulanui o Bergen. "I ka noiʻi o kēia manawa, pani mākou i ka pōʻai ma ka hoʻopili ʻana i kēia mau ʻike lapaʻau. Kūlike ʻole i kā mākou mea i manaʻo ai, ua hoʻopunipuni ʻia kahi enzyme digestive maʻamau no ka ʻōpū e komo i loko o ka moku pancreatic i loko o ka maʻi maʻi, i ka hopena e hoʻololi i ka huna ʻana o ka insulin.
I kēia lā, mālama ʻia ka poʻe me MODY8 me ka insulin a i ʻole nā lāʻau maʻi diabetes waha. E ʻimi ʻo Kulkarni a me kāna mau hoa hana i nā ala e hoʻolālā ai i nā lāʻau lapaʻau kūpono a pilikino. "No ka laʻana, hiki iā mākou ke hoʻopau i kēia mau ʻāpana protein, a i ʻole e kaupalena i kā lākou hōʻuluʻulu ʻana i ka cell beta?" wahi āna. "Hiki iā mākou ke lawe i nā ʻike mai nā mea i aʻo ʻia i nā maʻi ʻē aʻe e like me ka maʻi o Alzheimer a me ka maʻi o Parkinson i loaʻa kahi ʻano hoʻohui like i nā cell."
He aha e lawe ʻia mai kēia ʻatikala:
- When beta cells were bathed in solution from either mutated or normal exocrine cells, the beta cells took up both the mutated and normal proteins, bringing in higher numbers of the mutated proteins.
- But in one form of MODY called MODY8, a mutated gene in nearby exocrine cells is known to kick off this damaging process, said Kulkarni, corresponding author on a Nature Metabolism paper presenting the work.
- “Even in that scenario, she could show that the mutated protein is again taken up more by the beta cell in comparison to the normal protein, and it forms insoluble aggregates,”.
